The R-rated movie will star TJ Miller and Nick Swardson as two slackers who go to Hell to save their best friend.
Sarandon will voice the role of Barb the Angel in the upcoming animated feature, Deadline reports.
Hell & Back is currently in production.
Also voicing roles are American Pie star Jennifer Coolidge, Maria Bamford and Mila Kunis.
Hell & Back is being produced by ShadowMachine, which is behind the Adult Swim shows Robot Chicken and Moral Orel.
It will be directed by former Saturday Night Live writer Tom Gianas and Ross Shuman, a former set construction supervisor on Robot Chicken.
Sarandon also recently joined the upcoming drama The Big Shoe, also starring Jim Sturgess.