<p>Diabetes mellitus and periodontitis share inflammatory and oxidative pathways, creating a bidirectional relationship that aggravates both conditions. Melatonin, a hormone with antioxidant and immunomodulatory properties, is detectable in saliva and may serve as a non-invasive biomarker. However, its concentrations in individuals affected by both diabetes and periodontitis remain unclear. To evaluate whether salivary melatonin levels differ between adults with diabetes and periodontitis compared with healthy controls. A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251128090). PubMed, EMBASE and the Cochrane Library were searched up to August 2025 for observational studies assessing salivary melatonin in adults with diabetes and periodontitis versus healthy individuals. Data extraction and risk of bias assessment were performed independently by two reviewers. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. From 79 retrieved records, three cross-sectional studies involving 183 participants (103 patients with diabetes and periodontitis, 80 healthy controls) met the inclusion criteria. Pooled analysis revealed significantly lower salivary melatonin levels in affected patients compared with controls (MD: −2.74 pg/mL; 95% CI: −4.78 to − 0.71; <i>p</i> = 0.008). Substantial heterogeneity was observed (I² = 96%), likely due to methodological and population differences, but the direction of effect was consistent across all studies. Adults with diabetes and periodontitis exhibit reduced salivary melatonin concentrations compared with healthy individuals. These findings support the potential of salivary melatonin as a biomarker linking metabolic and periodontal health, although further high-quality studies with standardised protocols are needed to validate its clinical utility.</p>