The comedy stars No Ordinary Family's Michael Chiklis as a man called Vince who decides to take a more honest approach to life.
Deadline reports that Perkins will play Vince's wife, a teacher who deals patiently with his new candid personality.
Perkins previously played Celia in Weeds and recently worked on the upcoming movie Hop. She has also appeared in films such as Big and The Flintstones.
Vince Uncensored, which is being executive produced by Conan O'Brien's company Conaco, will be directed by Kelsey Grammer.