Antibiotic-associated diarrhea (AAD) is diarrhea caused by disturbances in intestinal microbiota and metabolism following inappropriate use of antibiotics. With the over-reliance on antibiotics, the incidence of AAD is increasing worldwide. Recently, the role of probiotics and prebiotic preparations in the prevention and treatment of AAD has received increasing attention. Various prebiotics can not only reduce the incidence of AAD, but also effectively shorten the course of the disease and alleviate the symptoms. Notably, many polysaccharides derived from plants and fungi are a class of biologically active and rich prebiotics with great potential to alleviate AAD. Therefore, this review aims to summarize the latest research on natural product polysaccharides to alleviate antibiotic-associated diarrhea by modulating the gut microbiota. It provides a theoretical basis for exploring the mechanism of natural product modulation of gut microbiota to alleviate AAD, and provides a reference for further development of active prebiotics.