The older adoptive half-sister of Sara, Melissa Gilbert is also an actress. Melissa's role in the television series Little House influenced Sara's career choice. At thirteen, she was awarded the role of Darlene Conner on the television series Roseanne, which she played until 1997. For this role she was nominated in 1993 and 1994 for an Emmy Award. In 1990 she was nominated for a Young Artist Award in the years 1991, 1992 and 1993, she won the prize. In 1997 she graduated with a degree in art and photography at Yale University with distinction.
Gilbert played in the thriller Poison Ivy - The Deadly Embrace (1992 ) alongside Drew Barrymore one of the main roles for which she was nominated for an Independent Spirit Award. In the comedy Desert Blue (1998) she starred alongside Kate Hudson and Christina Ricci in the movie the road with boys (2001) again alongside Drew Barrymore. From 2005 to 2006, she starred opposite Melanie Griffith in a leading role in the television series Twins. From 2007 to 2010, she starred in the series The Big Bang Theory as Dr. Leslie Winkle with. There she was initially listed only as a supporting role, then moved to the second season for the actress, which was, however, already made shortly thereafter reversed, so that Gilbert could concentrate on its position as the executive producer of the CBS talk show The Talk more.
Sara Gilbert and her former partner, the producer and writer Allison Adler, with whom she lived in a relationship from 2002, have a son born of Adler (* 2004) and one of Gilbert born daughter (* 2007). The couple separated in 2011. Since March 30, 2014, it is married to the songwriter and singer of 4 Non Blondes Linda Perry.