Speaking at the Carl von Ossietzky Medal Award Ceremony in Berlin in December 2010, Maguire imputed Criminal accountability to President Obama for violation of international law. "When President Obama says he wants to see a world without nuclear weapons and says, in respect of Iran and their alleged nuclear weapons ambitions, that 'all option [sic] are on the table,' this is clearly a threat to use nuclear weapons, clearly a Criminal threat against Iran, under the world court advisory opinion. The Nuremberg Charter of 8 August 1945 says the threat or use of nuclear weapons is Criminal, so officials in all nine nuclear weapons states who maintain and use nuclear deterrence as a threat are committing crimes and breaking international law."

Referring to the decision to award Mairead Maguire and Betty Williams the 1976 Nobel Peace Prize, Journalist Michael Binyon of The Times commented, "The Nobel committee has made controversial awards before. Some have appeared to reward hope rather than achievement." He described as sadly "negligible" the two women's contribution to bringing peace to Northern Ireland.

Maguire has received numerous awards and honours in recognition of her work. Yale University awarded Maguire an honorary Doctor of Laws degree in 1977. The College of New Rochelle awarded her an honorary degree 1978, as well. In 1998 Maguire received an honorary degree from Regis University, a Jesuit institution in Denver, Colorado. The University of Rhode Island awarded her an honorary degree in 2000. She was presented with the Science and Peace Gold Medal by the Albert Schweitzer International University in 2006, for meaningfully contributing to the spread of culture and the defence of world peace.

In January 1980, after a prolonged battle with depression over the loss of her children in the 1976 Finaghy Road incident, Mairead Maguire's sister Anne committed suicide. A year and a half later, in September 1981, Mairead married Jackie Maguire, who was her late sister's widower. She has three stepchildren and two children of her own, John Francis (b. 1982) and Luke (b. 1984).

In 1981 Maguire co-founded the Committee on the Administration of Justice, a nonsectarian organisation dedicated to defending human rights.

Mairead Maguire first visited Israel at age 40 in 1984. She came then as part of an interfaith initiative seeking forgiveness from Jews for years of persecution by Christians in Jesus' name. Her second visit was in June 2000, this time in response to invitations from Rabbis for Human Rights and the Israeli Committee Against House Demolitions. The two groups had taken upon themselves to defend Ahmed Shamasneh in an Israeli military court against charges of illegally constructing his home in the West Bank town of Qatanna, and Maguire traveled to Israel to observe the court proceedings and support the Shamasneh family.

Mairead Maguire has been a vocal supporter of Mordechai Vanunu, a former Israeli nuclear technician who revealed details of Israel's nuclear defence program to the British press in 1986 and subsequently served 18 years in prison for treason. Maguire flew to Israel in April 2004 to greet Vanunu upon his release and has since flown to meet with him in Israel on several occasions.

In 1990 she was awarded the Pacem in Terris Award, named after a 1963 encyclical letter by Pope John XXIII that called upon all people of good will to secure peace among all nations. The Davenport Catholic Interracial Council extolled Maguire for her peace efforts in Northern Ireland and for being "a global force against violence in the name of religion." Pacem in terris is Latin for "Peace on Earth".

The Nuclear Age Peace Foundation honoured Maguire with the Distinguished Peace Leadership Award in 1992, "for her moral leadership and steadfast commitment to social justice and nonviolence."

Maguire has been involved in a number of campaigns on behalf of political prisoners around the world. In 1993 she and six other Nobel Peace Prize laureates tried unsuccessfully to enter Myanmar from Thailand to protest the protracted detention of opposition leader Aung San Suu Kyi. She was a first signatory on a 2008 petition calling on Turkey to end its torture of Kurdish leader Abdullah Öcalan. In October 2010, she signed a petition calling on China to release Nobel Peace Prize laureate Liu Xiaobo from house arrest.

Mairead Maguire voiced strong opposition to the U.N. sanctions against Iraq, which is alleged by some to have resulted in hundreds of thousands of civilian deaths, calling them "unjust and inhuman," "a new kind of bomb," and "even more cruel than weapons." During a visit to Baghdad with Argentinian colleague Adolfo Pérez Esquivel in March 1999, Maguire urged then-U.S. President Bill Clinton and British Prime Minister Tony Blair to end the bombing of Iraq and to permit the lifting of U.N. sanction. "I have seen children dying with their mothers next to them and not being able to do anything," Maguire said. "They are not Soldiers."

In the aftermath of al-Qaeda's attacks on the U.S. in September 2001, as it became clear that the U.S. would retaliate and deploy troops in Afghanistan, Maguire campaigned against the impending war. In India she claimed to have marched with "hundreds of thousands of Indian people walking for peace." In New York, Maguire was reported to have marched with 10,000 protesters, purportedly including families of 9/11 victims, as U.S. war planes were already en route to strike Taliban targets in Afghanistan.

Mairead Maguire was twice arrested in the United States. On 17 March 2003, she was arrested outside the United Nations headquarters in New York City during a protest against the Iraq War. Later that month, on 27 March, she was one of 65 anti-war protesters briefly taken into custody by police after penetrating a security barricade near the White House.

At a joint press conference with Mordechai Vanunu in Jerusalem in December 2004, Maguire compared Israel's nuclear weapons to the Nazi gas chambers in Auschwitz. "When I think about nuclear weapons, I've been to Auschwitz concentration camp." She added, "Nuclear weapons are only gas chambers perfected ... and for a people who already know what gas chambers are, how can you even think of building perfect gas chambers."

In a speech delivered in February 2006 to the Nuclear Age Peace Foundation in Santa Barbara, California, Maguire again made a comparison between nuclear weapons and the Nazis. "Last April some of us protested at Dimona Nuclear Plant, in Israel, calling for it to be open to UN Inspection, and bombs to be destroyed. Israeli Jets flew overhead, and a train passed into the Dimona nuclear site. This brought back to me vivid memories of my visit to Auschwitz concentration camp, with its rail tracks, trains, destruction and death."

On 20 April 2007, Maguire participated in a protest against the construction of Israel's separation barrier outside the Palestinian village of Bil'in. The protest was held in a no-access military zone. Israeli forces used tear-gas grenades and rubber-coated bullets in an effort to disperse the protesters, while the protesters hurled rocks at the Israeli troops, injuring two Border Guard policemen. One rubber bullet hit Maguire in the leg, whereupon she was transferred to an Israeli hospital for treatment. She was also reported to have inhaled large quantities of tear gas.

In October 2008, Maguire arrived in Gaza aboard the SS Dignity. Although Israel had insisted that the yacht would not be permitted to approach Gaza, then-Prime Minister Ehud Olmert ultimately capitulated and allowed the ship to sail to its destination without incident. During her stay in Gaza, Maguire met with Hamas leader Ismail Haniyeh. She was photographed accepting an honorary golden plate depicting the Palestinian flag draped over all of Israel and the occupied territories.

In the wake of the 2009 Gaza flotilla, Ben-Dror Yemini, a popular columnist for the Israeli daily Ma'ariv, wrote that Maguire was obsessed with Israel. "There is a lunatic coalition that does not concern itself with the slaughtered in Sri Lanka or with the oppressed Tibetans. They see only the struggle against the Israeli Satan." He further charged that Maguire chose to identify with a population that elected an openly antisemitic movement to lead it – one whose raison d'etre is the destruction of the Jewish state.

In a 4 October 2010 editorial entitled "The disingenuous Nobel laureate," The Jerusalem Post called Maguire's comparison of Israel's nuclear weapons to the gas chambers of Auschwitz "outrageous" and maintained that "Israel can and must use its sovereignty to stop people like Maguire who are essentially seeking to endanger the lives of Israeli citizens." The Post applauded Maguire's expulsion from Israel, "not because of Maguire's outrageous comparison in 2004 of Israel’s purported nuclear capability to Auschwitz’s gas chambers, nor because of her absurd, reprehensible accusation made in court Monday that Israel is an “apartheid state” perpetrating “ethnic cleansing against Palestinians,” but because she had taken “actions that undermine Israel’s ability to protect itself.”

Maguire has more than once suggested that Palestinians are more interested in peace than Israelis are. She said in a 2011 interview that when she and some colleagues left Gaza in 2008, "we were very hopeful because there is a passionate Desire among the Palestinian people for peace," but "then Operation Cast Lead started the following week. That was horrific. It was devastating." Israel, she said, had killed Palestinian farmers and fishermen who were just "trying to fish for their families," thus proving "that the Israeli government does not want peace." In a 2013 interview, she repeated the same point, saying that in Gaza in 2008, she had been told by Hamas and Fatah Leaders "that they want dialogue and peace," yet a week later "Israel bombed Gaza, committing war crimes," showing "that there is no political will for peace in the Israeli government."

In October 2012, Maguire traveled to New York City to serve on the Russell Tribunal on Israel/Palestine alongside Writer Alice Walker, Activist Angela Davis, former Congresswoman Cynthia McKinney, and Pink Floyd’s Roger Waters. During her participation in the Russell Tribunal, Maguire, according to one report, "asked the question that seems to be taboo in the U.S.: Why does President Barack Obama allow Israel to threaten Iran with war when Iran has signed the NPT and Israel has at least 200 nuclear weapons? Why does the President not demand that Israel sign the NPT?"

In May–June 2010, Maguire was a Passenger on board the MV Rachel Corrie, one of seven vessels that were part of the Gaza Freedom Flotilla, a flotilla of pro-Palestinian Activists that attempted to bust the Israeli-Egyptian blockade of the Gaza Strip. In an interview with BBC Radio Ulster while still at sea, Maguire called the blockade an "inhumane, illegal siege." Having been delayed due to mechanical problems, the Rachel Corrie did not actually sail with the flotilla and only approached the Gazan coast several days after the main flotilla did. In contrast with the violence that characterised the arrival of the first six ships, Israel's takeover of the Rachel Corrie was met only with passive resistance. Israeli naval forces were even lowered a ladder by the passengers to assist their ascent onto the deck. After the incident, Maguire said she did not feel her life was in danger as the ship's captain, Derek Graham, had been in touch with the Israeli navy to assure them that there would be no violent resistance.

In March 2014, Maguire tried to arrive to Gaza through Egypt, as a part of Activist delegation which also included the American anti-war Activist Medea Benjamin. The members of the delegation were arrested in Cairo, questioned and deported.

In 2015, Maguire spoke with Democracy Now in a sit-down interview titled, "No to Violence, Yes to Dialogue," which included two other Nobel Peach Prize Laureates, Jody Williams and Leymah Gbowee. Maguire discussed the Desire "to end militarism and war, and to build peace and international law and human rights and democracy."

In 2016, Maguire attempted to break Israel's naval blockade of the Gaza Strip along with 13 other Activists, until they were stopped by the Israeli Navy approximately 40 miles offshore. The boat was escorted to the port of Ashdod. The Israeli military said the interception was brief and without injuries. Maguire complained that she and the Activists were "arrested, kidnapped, illegally, in international waters and taken against our wishes to Israel."

The Post argued that if Maguire and others “truly Desire to improve the lives of Gazans, they should send their humanitarian aid in coordination with Israel,” pressure Hamas “and the other radical Islamists who control the Gaza Strip to stop senseless ballistic attacks on Israeli towns and villages, kibbutzim and moshavim,” and “insist that Hamas provide Gaza’s citizens with a stable, responsible leadership that respects human rights and religious freedom, as well as that it accept the UN-recognized right of the Jewish people to self-determination and political sovereignty in their historical homeland.” But Maguire “seems more intent on enabling Israel’s terrorist enemies,” exploiting “charges of a 'humanitarian crisis' in Gaza in order to empower Hamas terrorists.” Jewish and Israeli opinion is not all negative. Following the June 2010 Gaza flotilla raid, Israeli Prime Minister Benjamin Netanyahu was careful to distinguish between Mairead Maguire's nonviolent resistance aboard the Rachel Corrie, which he referred to as "a flotilla of peace Activists – with whom we disagree, but whose right to a different opinion we respect," and the conduct of the Activists aboard the other six vessels, which he described as "a flotilla of hate, organized by violent, terrorism-supporting extremists." Gideon Levy strongly defended Mairéad Maguire in the Israeli newspaper Haaretz in October 2010, calling her "the victim of state terror" after Israel refused to allow her to enter the country and kept her detained for several days.