She has acted in the movies, Kissing Jessica Stein, Mo' Money, Garden State, Down, Queer Duck: The Movie, Legally Blonde 2: Red, White and Blonde, and A Dirty Shame and was the voice of the Water Cooler in Robots.
In addition to cameoing on the television show Curb Your Enthusiasm, she has appeared in many series, including Strangers with Candy, Hope and Faith, Ed, Starved, Cosby, 30 Rock, One Life to Live and was the voice of Dilmom on Dilbert.
Hoffman provided the voice of "Mary Phillips, the Talk Radio host", in the video game Grand Theft Auto: San Andreas. Despite her frequent stage banter on her dislike of children, Hoffman did a surprising turn as the voices of the Gate to Fairy-tale Land and the Witch's Magic Wand in the Dora the Explorer movie Dora's Fairytale Adventure. She has also been a frequent guest on Late Night with Conan O'Brien.