Background: Dental caries, periodontal disease, and oral cancer represent some of the most prevalent oral health problems globally, often detected at advanced stages when treatment options are more complex and outcomes less favorable. Saliva, as a non-invasive and easily accessible biofluid, has emerged as a promising medium for early disease detection through specific biomarkers reflecting oral and systemic health status. Objective: This study aimed to evaluate and compare salivary biomarkers—pH, buffering capacity, calcium, total protein, IL-6, TNF-α, and MMP-8 among patients with dental caries, periodontitis, and oral cancer, relative to healthy controls, to assess their diagnostic value for early detection. Methods: A cross-sectional analytical study was conducted between March and November 2024 at a dental teaching hospital. A total of 150 participants aged 20–65 years were recruited and divided into four groups: healthy controls (n=40), dental caries (n=40), periodontitis (n=40), and oral cancer (n=30). Unstimulated saliva samples were collected and analyzed for pH, buffering capacity, calcium, total protein, IL-6, TNF-α, and MMP-8 using standardized laboratory methods. Data were analyzed using ANOVA and ROC curve analysis (SPSS v26), with a significance level of p < 0.05. Results: No significant differences were found in age or gender distribution across the groups (p > 0.05). Salivary pH and buffering capacity were significantly lower in the caries group (p < 0.001), indicating higher acidogenicity. IL-6, TNF-α, and MMP-8 levels were markedly elevated in the periodontitis and oral cancer groups (p < 0.001), reflecting strong inflammatory activity. ROC analysis revealed IL-6 (AUC 0.87), MMP-8 (AUC 0.84), and TNF-α (AUC 0.81) as the most accurate biomarkers for differentiating diseased from healthy individuals. Conclusion: Salivary biomarkers, particularly IL-6, TNF-α, and MMP-8, demonstrated excellent diagnostic potential for early detection of oral diseases. Their non-invasive nature and high discriminatory power highlight saliva’s utility as a rapid, cost-effective screening tool in clinical and community settings.