The pop star will appear as a Christian conservative sidekick to Sean Hayes' character, Jack, who hosts his own talk show, on the April 13 episode, the network said.
Jack's fictional network, Out TV, is bought by a Christian TV network, leading to Spears contributing a cooking segment called "Cruci-fixin's."
As a young girl, the 24-year-old Spears was a regular on "The Mickey Mouse Club." After becoming a pop singer, she starred in the critically panned 2002 film "Crossroads."
Last September, Spears gave birth to her first child, son Sean Preston, with husband Kevin Federline.
"Will & Grace," which also stars Eric McCormack, Debra Messing and Megan Mullally, is in its eighth and final season. It airs Thursdays at 8 p.m. (EST).