Oral cancer, a leading cause of mortality, requires early detection for effective treatment. Traditional diagnostic methods, such as biopsy and histopathological analysis, face limitations in terms of invasiveness and the timing of detection. This study investigates the integration of salivary biomarkers with histopathological analysis for the early diagnosis of oral cancer. The objective was to assess the diagnostic accuracy of salivary biomarkers, specifically focusing on their correlation with histopathological findings. The study utilized a cohort of 120 participants, categorized into three groups: oral cancer patients, patients with premalignant lesions, and a control group. Statistical analyses, including ANOVA and correlation tests, revealed significant differences in salivary biomarker levels among the groups. The salivary biomarkers demonstrated high sensitivity and specificity for detecting oral cancer, with a diagnostic accuracy rate of 85%. The histopathological analysis supported the salivary biomarker findings, reinforcing their potential as a complementary tool for early detection. This approach holds promise in enhancing non-invasive diagnostic methodologies and may facilitate earlier intervention in at-risk populations. Future research should focus on validating these findings in larger cohorts and exploring the underlying molecular mechanisms of the identified biomarkers.