Kidder's international breakthrough came with playing Lois Lane in Superman (1978) and Kathy Lutz in The Amityville Horror (1979), which were blockbuster films.

After a stint of films and projects that were ambivalently received, Kidder sustained serious injuries in a car accident that left her temporarily paralyzed in 1990, and suffered from a highly publicized manic episode and nervous breakdown in 1996 stemming from bipolar disorder.

[12] Kidder became interested in politics from a young age, which she credited to debates her parents would have over the dinner table; her mother had socialist leanings, while her father was a conservative Republican.

[25] After moving to Los Angeles, Kidder was cast opposite Gene Wilder in Quackser Fortune Has a Cousin in the Bronx (1970)[26] as an exchange student in Ireland who becomes the love interest of a poor horse manure collector in Dublin whom she almost runs over with her car.

[27] A year later, she returned to California, and was cast in the Brian De Palma film Sisters (1972), which gained notoriety for both director and Kidder, who as leading lady, portrayed conjoined twins, one of whom is a suspect in a brutal murder.

"[34] In the summer of 1975, Kidder was hired to direct a documentary short chronicling the making of The Missouri Breaks (1976), a Western film starring Marlon Brando and Jack Nicholson.

[37] In 1977, eager to return to acting, Kidder read for the character of Lois Lane in Superman: The Movie, only one month before principal photography was scheduled to begin.

[41] James Harwood of Variety said that she "plays perfectly off both of his [Reeve's] personalities and her initial double-entendre interview with Superman is wickedly coy, dancing round the obvious question any red-blooded girl might ask herself about such a magnificent prospect.

"[42] Sonia Saraiya of Vanity Fair praised her ability to balance Lois's ditzy nature with her ambition and no-nonsense attitude, and wrote: "Kidder played a human woman who could believably both attract and deserve a man who is canonically perfect, with the physique of a Greek god and the moral compass of a saint.

"[49] Also in 1980, she appeared in Paul Mazursky's romantic comedy Willie & Phil, playing one-third of a love triangle opposite Michael Ontkean and Ray Sharkey.

[50] Kidder starred in the Canadian comedic road movie Heartaches (1981), portraying a free-spirited woman who helps an acquaintance raise her child.

"[51] She then starred opposite Richard Pryor in the comedy Some Kind of Hero (1982), about a Vietnam War veteran who attempts to re-assimilate into civilian life.

[53] In 1982, she appeared in a stage performance of Bus Stop, playing Cherie opposite Tim Matheson as Bo, which was broadcast on HBO.

The same year Superman III was released, Kidder also starred as a court stenographer-cum-private eye named Mickey Raymond in the comedy Trenchcoat (1983).

[57] In 1984, Kidder produced and starred in the French-Canadian period television film Louisiana as a plantation owner in the American South who returns from Paris to find her estate and holdings have been lost.

In 1985, Kidder expressed ambivalence toward continuing her career, and was quoted as saying: "I don't feel comfortable as a performer and I'm a big turkey as a movie star.

[59] Body of Evidence (1988), a CBS Movie of the Week, cast Kidder as a nurse who suspects that her medical pathologist husband is a serial killer.

This was followed by a role as a psychic in To Catch a Killer (1992), a Canadian television thriller film based on the crimes of John Wayne Gacy.

[68] Also that year she appeared in three episodes of Peter Benchley's Amazon, playing a striking role as an insane Canadian woman bent on domination of all the local tribes.

In 2006, Kidder played Jenny Schecter's mother Sandy Ziskin on The L Word; her character was a repressed Jewish woman coming to terms with her daughter's sexuality.

[70] In 2008, she portrayed an embattled guidance counselor in the gay-themed mystery film On the Other Hand, Death, as well as a supporting role as Laurie Strode's therapist, in Rob Zombie's Halloween II (2009).

[76] In a piece called "Confessions of 'Baghdad Betty'", styled as a letter to her mother and printed in The Nation, Kidder responded by explaining and defending her statements.

[87] When discussing sustainable energy, Kidder said: "The first thing people have to start facing, contrary to the advertising fed to us by oil and gas companies, is that environmentalism and economic stability go hand-in-hand on any long term basis.

[88] In addition to environmental causes, Kidder was a vocal supporter of LGBT rights, and in 2003 hosted benefits at a gay and lesbian health center in Boston, Massachusetts.

[14] In December 1990, Kidder was seriously injured in a car accident during the filming of the pilot of a proposed television series Nancy Drew and Daughter which left her partially paralyzed as a result of spinal injury.

[14][101] At the time, Kidder had been working on an autobiography when her laptop computer became infected with a virus, which caused it to crash and her to lose three years' worth of drafts.

She was later found by a homeowner in the backyard of a Glendale residence,[103] and was taken by the Los Angeles Police Department to Olive View–UCLA Medical Center in a distressed state, the caps on her teeth having been knocked out during a rape attempt.

[102] In a 2000 interview, Kidder stated that, in addition to suffering emotional distress, her manic episodes had led her to experiencing significant financial woes: "I went through millions of dollars—I have no idea how much.

[108] Kidder's friends related that she had poor health in later years, particularly following her lengthy stay at the Standing Rock protest camp in 2016, often enduring frigid temperatures.

"[110][111] After her death, director Ted Geoghegan, who knew the actress, stated: Margot lived at the foot of Canyon Mountain, right outside of Livingston.