Abstract: Pandemic diseases pose a major threat to human health, life and economy in the world. Vaccines have been proved to be the most effective weapon for controlling and preventing pandemic diseases. As most pathogens invade the body through mucosal surfaces, mucosal vaccination can fundamentally prevent the spread of infectious pathogens by triggering the protective immunity at the mucosal sites. The application of biomaterials and advanced drug delivery technologies has ushered in a new era of mucosal vaccine development. Despite this, our knowledge of mucosal immunity remains limited, and considerable scientific challenges still remain unsettled in the development of mucosal vaccines. In this review, the latest progress of mucosal immune systems and the technological advancement of mucosal vaccine delivery are summarized, aiming to provide innovative strategies to facilitate the design and development of rational mucosal vaccine against infectious diseases.