[1] Following appearances in television movies and a commercial for Kool-Aid, at 13 she landed the role of Darlene Conner, the sarcastic middle child, in Roseanne.

Her contribution was considered so important to Roseanne that the show's producers juggled storylines and taping schedules to allow her to study at Yale University while remaining in the cast, shooting remote segments of Darlene at a soundstage in New York.

[5] Gilbert has appeared on The Simpsons, 24, Will & Grace, Law & Order: Special Victims Unit and Private Practice.

Starting in 2004, she had a recurring role as smart and sarcastic medical student Jane Figler on the long-running hospital drama ER; her appearances spanned seasons 11–13.

Gilbert regained a regular spot on prime time television in the fall of 2005 in the sitcom Twins on The WB network.

The show was canceled after one season, when the WB and UPN networks merged as The CW and dropped a number of series.

However, on May 29, 2018, in the wake of controversial remarks made by Barr on Twitter regarding Valerie Jarrett (an advisor to former president Barack Obama), ABC cancelled the revival after a single season.

That series, The Conners, featuring all of the regular cast except Barr, premiered in October 2018, with Gilbert starring and serving as an executive producer.

Gilbert appeared in two films alongside Drew Barrymore, in Poison Ivy in 1992 and Riding in Cars with Boys in 2001.

She has had several minor roles following Roseanne, including the short film $30 (aka 30 Bucks) as part of the Boys Life 3 feature, and High Fidelity.