Abstract: The oral mucosa is persistently subjected to an environment replete with a substantial quantity of microorganisms, allergens, other antigens, and high-frequency mechanical stimuli, yet it manages to maintain long-term stability. Serving as the body's primary immune barrier, the oral mucosal defense system assumes an indispensable role in upholding local and systemic immune homeostasis.The oral mucosal epithelium is characterized by a stratified squamous structure. Saliva, microorganisms, the epithelial barrier, diverse immune cells, and cytokines interact through a range of physical, chemical, and immunological mechanisms both on the outer mucosal surface and within the mucosal epithelium. These elements collaboratively constitute a multi-layered and intricate defense system. The present article aims to comprehensively review the recent research advancements in oral mucosal defense, with the intention of providing a framework for further exploration and elucidation of the complex underlying mechanisms.