Queen Isabella appeared with a major role in Christopher Marlowe's play Edward II (c. 1592) and thereafter has been frequently used as a character in plays, books, and films, often portrayed as beautiful but manipulative or wicked. Thomas Gray, the 18th-century poet, combined Marlowe's depiction of Isabella with william Shakespeare's description of Margaret of Anjou (the wife of Henry VI) as the "She-Wolf of France", to produce the anti-French poem The Bard (1757), in which Isabella rips apart the bowels of Edward II with her "unrelenting fangs". The "She-Wolf" epithet stuck, and Bertolt Brecht re-used it in The Life of Edward II of England (1923).

In Derek Jarman's film Edward II (1991), based on Marlowe's play, Isabella is portrayed (by Actress Tilda Swinton) as a "femme fatale" whose thwarted love for Edward causes her to turn against him and steal his throne. In contrast to the negative depictions, Mel Gibson's film Braveheart (1995) portrays Isabella (played by the French Actress Sophie Marceau) more sympathetically. In the film, an adult Isabella is fictionally depicted as having a romantic affair with the Scottish hero william Wallace. However, in reality, she was nine years old at the time of Wallace's death. Additionally, Wallace is incorrectly suggested to be the father of her son, Edward III, despite Wallace's death being many years before Edward's birth.

The retribution began immediately. Hugh Despenser the elder had been captured at Bristol, and despite some attempts by Isabella to protect him, was promptly executed by his Lancastrian enemies – his body was hacked to pieces and fed to the local dogs. The remainder of the former regime were brought to Isabella. Edmund Fitzalan, a key supporter of Edward II and who had received many of Mortimer's confiscated lands in 1322, was executed on 17 November. Hugh Despenser the younger was sentenced to be brutally executed on 24 November, and a huge crowd gathered in anticipation at seeing him die. They dragged him from his horse, stripped him, and scrawled Biblical verses against corruption and arrogance on his skin. He was then dragged into the city, presented to Queen Isabella, Roger Mortimer, and the Lancastrians. Despenser was then condemned to hang as a thief, be castrated, and then to be drawn and quartered as a traitor, his quarters to be dispersed throughout England. Simon of Reading, one of the Despensers' supporters, was hanged next to him, on charges of insulting Isabella. Once the core of the Despenser regime had been executed, Isabella and Mortimer began to show restraint. Lesser nobles were pardoned and the clerks at the heart of the government, mostly appointed by the Despensers and Stapleton, were confirmed in office. All that was left now was the question of Edward II, still officially Isabella's legal husband and lawful king.