She was briefly married to actor Bert Remsen, one month her junior, in 1949-50, and to actor, Director and Teacher Edward G. Kaye-Martin, 14 years her junior, from August 1969 to October 1970.

Beginning in the 1950s, as Scottie MacGregor, she worked in theatre on and off Broadway in New York and other states in plays such as The Seven Year Itch and Handful of Fire, and won such uncredited parts as "a longshoreman's mother" (On the Waterfront); "Alice Thorn" (The Traveling Executioner) and "Miss Boswell" (The Student Nurses). She appeared in numerous episodes of various television series: Love of Life (1956), Play of the Week (1959), East Side/West Side (1963), Mannix (1970–71), Emergency! (1972), Ironside (1972, 1974), and All in the Family (1973), as well as the two 1981 "Heroes vs. Villains" episodes of Family Feud hosted by Richard Dawson. She had roles in the TV movies, The Death of Me Yet (1971), The Girls of Huntington House (1973), and Tell Me Where It Hurts (1974).

In 1974 she began her role as the general store owner's wife, Harriet Oleson on NBC's Little House on the Prairie. MacGregor's favorite description of her character in Little House came in a fan letter from Minnesota in the 1970s, in which Mrs. Oleson was described as "the touch of pepper in the sweetness of the show". In 1979, thanks to the popularity of Little House in Spain, MacGregor was invited to Madrid, Spain and appeared on RTVE's 625 Lineas program. After Little House on the Prairie, she withdrew from screen productions in favor of local theater. She dedicated herself to the Hindu religion, and to teaching acting to children at the Wee Hollywood Vedanta Players, before finally retiring in the early 2000s.