Based on the book series by Vicky Iovine, Girlfriends' Guide to Divorce follows a best-selling author (Lisa Edelstein) of a self-help book series who is secretly hiding her separation from her husband as she starts to navigate her life as a single woman in her 40's in Los Angeles. She starts to side with and accept advice more from her divorced friends rather than her married ones, which leads to unexpected and life-altering experiences.