On Saturday, the actor shared a sketch of an angry-looking woman with the caption, "This is the portrait of a so-called Christian whose only purpose in life is to lie for the wicked. Monstrous!"
Carrey's rep confirmed the sketch was the actor's artistic work, but there was no comment on whether it was in fact the White House press secretary.
Many Twitter users, however, thought it shared her likeness and immediately clapped back at "The Truman Show" star.
One Twitter user wrote, "Apparently you misunderstand the definition of Christian. It's certainly not what #Hollywood thinks!"
Another added, "This is one more reason that I'm done with Hollywood. It's ok to be mean and hurtful as long as it's to someone you disagree with, right?"
A request for comment from Sanders and the White House was not immediately returned to ABC News. Sanders' father, Mike Huckabee, the former governor of Arkansas, defended his daughter on social media.
"Pathetic BULLY, sexist, hater, bigot & "Christaphobe" @jimcarrey attacks @PressSec for her faith; what would be hypocritical Hollywood reaction if he called someone a 'so-called Muslim' or 'so-called Jew?' #classlessCarrey," he wrote.
Carrey did have his share of supporters.
"People can paint whoever or whatever whenever they want. Don't like it, don't look at it. Good for you Jim Carrey artistic expression is a wonderful thing no matter what the form," one person said.
The portrait isn't the first Carrey has shared on his Twitter feed. He posted a flattering one of the late Stephen Hawking last week, praising the physicist after his death.
"Cheers to you Stephen Hawking, the greatest mental athlete of our time. You are all that is! See you around, buddy! ;^)," he wrote.
Other pictures shared by Carrey include Marco Rubio and President Donald Trump.