BACKGROUND AND OBJECTIVE: Proinflammatory cytokines and enzymes responsible for tissue destruction are important in the development of periodontitis. This study compared salivary concentrations of interleukin-1 beta (IL-1β), matrix metalloproteinases (MMP-8), and (MMP-9) in individuals with and without periodontitis to evaluate their diagnostic utility as potential biomarkers. MATERIALS AND METHODS: A comprehensive search was performed across PubMed, Scopus, ScienceDirect, and Google Scholar, supplemented by manual searches in relevant journals up to January 2024. Eligibility criteria focused on human studies with defined diagnostic criteria for periodontitis and saliva samples analyzed for IL-1β, MMP-8, and MMP-9. Data were extracted to compare salivary levels of these markers between periodontitis patients and healthy controls. The Joanna Briggs Institute tool was used to evaluate the risk of bias and quality of the included studies. Statistical analysis employed a random effects model to calculate standardized mean differences and assess heterogeneity and publication bias. RESULTS: The search yielded 122 articles, with 27 meeting the inclusion criteria. Fifteen percent of these studies presented a moderate risk of bias, while the remaining 85% exhibited a low risk of bias. The meta-analyses indicated significantly higher levels of IL-1β, MMP-8, and MMP-9 in the saliva of subjects with periodontitis compared to healthy individuals: IL-1β: Standardized Mean Difference (SMD) = 163.29 (95% CI = 104.64-221.95), p <
0.002
MMP-8: SMD = 282.22 (95% CI = 209.68-354.77), p <
0.002
MMP-9: SMD = 311.85 (95% CI = 179.64-444.05), p <
0.002. CONCLUSION: Elevated salivary levels of IL-1β, MMP-8, and MMP-9 are linked to periodontitis.