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Early diagnosis of oral and systemic diseases remains a major challenge due to limitations in conventional invasive procedures. This review addresses the critical need for non-invasive, accessible diagnostics by examining the potential of saliva as an alternative diagnostic fluid. The main objective is to synthesize current knowledge on salivary biomarkers and technological innovations that enhance early detection capabilities. Methodologically, the review integrates evidence from proteomic, genomic, and metabolomic studies, as well as recent advances in microfluidic point-of-care devices. Key findings highlight that saliva contains a rich array of biomarkers, including cytokines, microRNAs, and extracellular vesicles, that can accurately reflect both local oral pathologies, such as dental caries and oral cancer, and systemic conditions, including diabetes, cardiovascular diseases, autoimmune disorders, and neurodegenerative diseases. The analysis further emphasizes that portable biosensors and lab-on-chip platforms are rapidly improving diagnostic sensitivity and enabling decentralized testing. Notwithstanding these encouraging advancements, issues with biological variability, standardization, and regulatory validation still exist. This review underscores the significance of interdisciplinary collaboration to overcome these barriers and fully integrate salivary diagnostics into routine healthcare. The implications are profound: widespread adoption could transform preventive medicine by providing patient-friendly, real-time monitoring tools that improve health outcomes globally.