Abstract: The significance of microbiota in regulating mucosal homeostasis has been addressed intensively in recent years. Meanwhile, research on human microorganism communities and their interaction with the immune system has achieved great advancement. As an essential component of the human microbiota, the gut commensal flora plays a unique role in maintaining a sophisticated balance between host defense and immune tolerance. Dysbiosis of gut microbiota may result in alterations of the innate immune system via multiple strategies. This review summarizes the underlying mechanisms of the interplay between microbiota and the innate immune system, focusing on gut-associated lymphoid tissue, innate lymphoid cells, and phagocytes.