Perlman began acting in the early 1970s with numerous appearances on TV films and short films. One of her first notable parts was a recurring role on the television show Taxi as Zena, girlfriend of Louie DePalma (played by Danny DeVito).
Perlman’s motion picture roles included There Goes The Neighborhood (1992), Canadian Bacon (1995), Carpool (1996), Sunset Park (1996), and Matilda (1996). She had a cameo in the film 10 Items Or Less (2006), and also starred in the 2007 independent film Love Comes Lately.
She later starred in the 1996 sitcom Pearl as the title character and was featured on the 2001 TV drama Kate Brasher. Among her notable guest appearances was on the season 4 premiere of Becker, which starred Cheers co-star Ted Danson.
Since 2014, she has starred in a recurring role on The Mindy Project as Danny’s mother Annette Castellano.