Edible mushrooms have been an important part of the human diet for thousands of years, and over 100 varieties have been cultivated for their potential human health benefits. In recent years, edible mushroom polysaccharides (EMPs) have been studied for their activities against obesity, inflammatory bowel disease (IBD), and cancer. Particularly, accumulating evidence on the exact causality between these health risks and specific gut microbiota species has been revealed and characterized, and most of the beneficial health effects of EMPs have been associated with its reversal impacts on gut microbiota dysbiosis. This demonstrates the key role of EMPs in decreasing health risks through gut microbiota modulation effects. This review article compiles and summarizes the latest studies that focus on the health benefits and underlying functional mechanisms of gut microbiota regulation via EMPs. We conclude that EMPs can be considered a dietary source for the improvement and prevention of several health risks, and this review provides the theoretical basis and technical guidance for the development of novel functional foods with the utilization of edible mushrooms.