Background: Oral squamous cell carcinoma (OSCC) remains a major global health burden due to delayed diagnosis. Although salivary biomarkers have been explored in previous meta-analyses, these studies were limited to specific biomarker types. Methods: This study followed PRISMA guidelines and was registered in PROSPERO (CRD 420261296936). PubMed, Scopus, MEDLINE, and CINAHL were searched for diagnostic accuracy studies of salivary biomarkers for OSCC. Studies providing sufficient data to construct 2 × 2 tables were included. Pooled sensitivity, specificity, DOR, and HSROC curves were estimated using a bivariate random-effects model, and study quality was assessed using QUADAS-2. Results: Eighteen studies comprising 1647 participants yielded 45 diagnostic datasets across multiple biomarker classes. The pooled sensitivity and specificity were 0.64 (95% CI: 0.59–0.69) and 0.71 (95% CI: 0.66–0.76), respectively. The pooled DOR was 4.53 (95% CI: 3.18–6.47), indicating moderate discriminatory ability, with an AUC of 0.75 (95% CI: 0.71–0.79). Fagan’s nomogram analysis demonstrated that these biomarkers are not suitable for screening the general population and should be reserved for enriched populations (pre-test probability > 10%). Conclusions: Salivary biomarkers demonstrate moderate but highly heterogeneous diagnostic accuracy. Clinical utility is context-dependent and limited to enriched populations with a baseline probability of OSCC >10%. In screening the general population (prevalence < 0.01%), these tests offer no significant clinical utility. They should be considered complementary triage tools rather than definitive diagnostic modalities. © 2026 by the authors.