Milano will appear in the recurring role of Billie, a woman inspired by the karma-seeking ways of Earl Hickey (Jason Lee) to clean up her own act.
Her first appearance -- along with that of fellow guest star Michael Rapaport ("The War at Home") -- is scheduled for early October, Zap2it.com reported Wednesday.
Rapaport will play Earl's old acquaintance and fellow prison inmate.
"We have two very strong actresses (Jaime Pressly and Nadine Velazquez) on the show, so when we were going to bring in a third for a few episodes, we knew we had to get someone with some real presence," series creator Greg Garcia told the Web site. "Alyssa is a popular TV star, and we're delighted to have her join us for what will be a great storyline."