The twice-divorced pop icon will appear on a celebrity panel, along with Ricky Gervais and Larry David, to mediate warring couples. Panelists will watch footage of the feud and, after some deliberation, declare a "winner".
The Jerry Seinfeld created show will feature a cast of rotating weekly guests, including actors Alec Baldwin, Tina Fey, and Eva Longoria.
Madonna, who divorced film director Guy Richie in 2008 and actor Sean Penn in the early nineties, rarely makes television appearances other than for musical performances or interviews.
The episode will film before a live studio audience in New York City next week. The series premieres on NBC February 28.