Gershon was born in Los Angeles, California, the daughter of Mickey (née Koppel), an interior decorator, and Stan Gershon, who worked in import/export business and sales. Gershon is Jewish, and has a brother, Dann, and a sister, Tracy. She attended Beverly Hills High School with Lenny Kravitz. After high school, Gershon moved to Boston, where she attended Emerson College.

A 2008 Vanity Fair article linked her romantically with former President Bill Clinton. Speaking on the U.S. television show Live with Regis and Kelly on June 9, she said, "It is such a crazy, outrageous lie.... I met him three times at events. It disturbed me on so many levels. I felt I had to stand up and say the truth."

Gershon has dated hotel owner Sean McPherson, wealthy entrepreneur Jay Penske, and actors John Cusack and Owen Wilson.