Boyle's first film role was a bit part in Ferris Bueller's Day Off (1986), which earned her a SAG card, though her scene was eliminated from the final cut of the film. She then appeared in Amerika (1987), Poltergeist III (1988) and Dead Poets Society (1989), before landing her first major part, and the role which made her well known, playing Donna Hayward in the critically acclaimed series Twin Peaks. When the series ended in 1991, creator David Lynch produced a movie, Twin Peaks: Fire Walk With Me, but - largely due to her rise in fame, and increased film offers - Boyle chose not to return. Moira Kelly took over the role of Donna for the film.

Boyle spent much of the nineties making a name for herself in films with varying degrees of success. Some of her most notable roles were that of the obsessive and accident-prone Stacy in Wayne's World (1992) , the fragile, homeless teen Heather in Where The Day Takes You (1992) , psycho secretary-from-hell Kris Bolin in what was geared to be her breakout success, but ultimately became a box-office bust, The Temp (1993) , the sultry and manipulative Suzanne of Red Rock West (1993) which solidified her status as a premier femme fatale, Alex, the sexually assured drama queen in the cult classic Generation X comedy Threesome (1994) and flighty, manically repressed housewife Marianne Byron in Afterglow (1997).

Finally, in 1997, Boyle auditioned for the title role in David E. Kelley's Ally McBeal. Although she lost out to Calista Flockhart, Boyle impressed him enough to create the role of Assistant District Attorney Helen Gamble in his other 1997 series, The Practice specifically for her. She starred on the show until 2003, when - in a dramatic attempt to revamp the show and cut costs - she was unceremoniously dismissed along with most of the other main cast. The role of Helen earned her an Emmy nomination, as well as household fame and several Screen Actors Guild ensemble cast nominations. She also made a crossover appearance in the role of Helen in an episode of Ally McBeal.

In 2002, Boyle played a lead role in the blockbuster film Men in Black II as the villainous alien Serleena. She also guest starred on one of the last episodes of Ally McBeal once again, only this time as Tally Cupp, a completely different role from that which she played before.

Recently, she had a recurring role on several episodes of Huff, playing Melody Coatar, an unstable bipolar manic-depressive .

In 2005, Boyle joined the cast of Las Vegas for a seven episode stint as Monica, a new hotel owner.

Boyle has dated actors Jack Nicholson, Richard Dean Anderson, Kyle MacLachlan and David Spade, has a tattoo on her back from boyfriend Jay Penske, and was married for two years to John Patrick Dee III.