Boyle was born in Davenport, Iowa, the daughter of Sally, a clerical worker, assistant, and manager, and Michael L. Boyle. Her paternal grandfather was U.S. Representative Charles A. Boyle. She has German, Irish, and Italian ancestry. She is named after a character in Boris Pasternak's novel Doctor Zhivago. She was raised in Chicago, Illinois and Wisconsin. She graduated from The Chicago Academy for the Arts.
Boyle's first film role was a small part in Ferris Bueller's Day Off (1986), which earned her a SAG card, though her scenes were deleted from the final cut of the film. She then appeared in the miniseries Amerika (1987) and feature film Poltergeist III (1988). Although she was cast in Dead Poets Society (1989), her scenes were deleted.
Her first major role was as Donna Hayward in the critically acclaimed television series Twin Peaks (1990-1991). However, she was unable to reprise her role as Donna in the prequel film Twin Peaks: Fire Walk with Me (1992) due to scheduling conflicts with roles in other films such as Where the Day Takes You, Wayne's World, and Equinox. In 1993, Boyle was cast as Kris Bolin in The Temp and Suzanne in Red Rock West.
In 1994, Boyle was cast as Alex in the comedy Threesome. In 1997, she portrayed Marianne Byron in the film Afterglow. The following year, Boyle portrayed Helen Jordan in Happiness. In 1997, Boyle auditioned for the title role in David E. Kelley's Ally McBeal. Although she lost out to Calista Flockhart, the actress impressed Kelley enough to create the role of Assistant District Attorney Helen Gamble in his other 1997 series, The Practice, specifically for her. She starred on that show until 2003, when, in a dramatic attempt to revamp the show and cut costs, she was dismissed along with most of the cast. For her performance as Helen Gamble, she received an Emmy nomination as well as several Screen Actors Guild ensemble cast nominations. Boyle also made a crossover appearance in the role of Helen Gamble in an episode of Ally McBeal, and an uncredited guest appearance on the same show in its final season.
In 2002, Boyle played a lead role in the blockbuster feature film Men in Black II as the villainous shapeshifting alien Serleena. She also guest-starred on one of the last episodes of Ally McBeal, this time as Tally Cupp, and had a recurring role on several episodes of Huff. In 2005, Boyle joined the cast of Las Vegas for a seven-episode stint as Monica Mancuso, a new hotel owner. She played Barbara Amiel in the TV true story Shades of Black, about Amiel's controversial husband, Lord Conrad Black. Boyle also guest-starred as an ambitious reporter involved with the suspects in a possible murder in the Law & Order 2008 episode "Submission".
In 2009, Boyle portrayed Mary in Baby on Board. The same year, Boyle was cast as Betty McBain in the independent film Life Is Hot in Cracktown. In 2010, she starred as Kathy in Cougar Hunting. In 2013, Boyle portrayed Witch Agnes in the horror comedy film Hansel & Gretel Get Baked. In 2014, she portrayed Ms. Donley in the film Lucky Dog.
Boyle has been married twice. Her first husband was John Patrick Dee III, whom she married on August 11, 1996, and divorced two years later. Later, Boyle dated Jack Nicholson. They went public with their romance at the 1999 Emmys, and remained together until the end of 2000. Her current husband is Donald Ray Thomas II, a real-estate investor, whom she married on December 18, 2006, in San Antonio, Texas.