Mucosal surfaces as the largest immune organ of human body cover 400 m2 of the body including the gastrointestinal, urogenital, and respiratory tracts. The local mucosal immunity is an important first line of defense against many pathogens because most pathogens initiate their infection through access to the mucosal region of body. Also, the mucosal vaccines induce mucosal and systemic immunity simultaneously. Therefore, attracted by the advantages of mucosal immunity, researchers keep an eye on the mucoadhesive and pH-sensitive polymeric vaccine delivery system to solve several limitations of mucosal administration, making mucosal immunity receive great interests lately. In this review, we discuss natural polymer- and synthetic polymer-based mucoadhesive and pHsensitive systems used for mucosal vaccine delivery. Also, we cover how to target antigen presenting cells and M cells for the cell specificity. Finally, we conclude the significant progress in mucosal vaccine and the prospect mucosal vaccine research in the future.