This review comprehensively explores the intricate immune responses within the oral cavity, emphasizing the pivotal role of saliva in maintaining both oral and systemic health. Saliva, a complex biofluid, functions as a dynamic barrier against pathogens, housing diverse cellular components including epithelial cells, neutrophils, monocytes, dendritic cells, and lymphocytes, which collectively contribute to robust innate and adaptive immune responses. It acts as a physical and immunological barrier, providing the first line of defense against pathogens. The multifaceted protective mechanisms of salivary proteins, cytokines, and immunoglobulins, particularly secretory IgA (SIgA), are elucidated. We explore the natural and induced immune responses in saliva, focusing on its cellular and molecular composition. In addition to saliva, we highlight the significance of a serum-like fluid, the gingival crevicular fluid (GCF), in periodontal health and disease, and its potential as a diagnostic tool. Additionally, the review delves into the impact of diseases such as periodontitis, oral cancer, type 2 diabetes, and lupus on salivary immune responses, highlighting the potential of saliva as a non-invasive diagnostic tool for both oral and systemic conditions. We describe how oral tissue and the biofluid responds to diseases, including considerations to periodontal tissue health and in disease periodontitis. By examining the interplay between oral and systemic health through the oral-systemic axis, this review underscores the significance of salivary immune mechanisms in overall well-being and disease pathogenesis, emphasizing the importance of salivary mechanisms across the body.