Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose–Response Meta-Analysis

<b>Background/Objectives</b>: There is no definitive consensus regarding the effects of melatonin on cardiometabolic risk factors (CMRFs). This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the impacts of melatonin supplementation on CMRFs, including anthropometric, lipid, glycemic, inflammatory, oxidative, and liver function parameters. <b>Methods</b>: A systematic search across multiple databases retrieved 63 eligible RCTs published up to October 2025. <b>Results</b>: This random-effects meta-analysis indicated that melatonin supplementation significantly reduced hip circumference (weighted mean difference (WMD): -1.18 cm, 95% confidence interval (CI): -2.28, -0.08), systolic blood pressure (WMD: -2.34 mmHg, 95% CI: -4.13, -0.55), fasting blood glucose (WMD: -11.63 mg/dL, 95% CI: -19.16, -4.10), low-density lipoprotein cholesterol (WMD: -6.28 mg/dL, 95% CI: -10.53, -2.03), total cholesterol (WMD: -6.97 mg/dL, 95% CI: -12.20, -1.74), C-reactive protein (WMD: -0.59 mg/L, 95% CI: -0.94, -0.23), malondialdehyde (WMD: -1.54 μmol/L, 95% CI: -2.07, -1.01), tumor necrosis factor-alpha (WMD: -1.61 pg/mL, 95% CI: -2.31, -0.90), interleukin-6 (WMD: -6.43 pg/mL, 95% CI: -10.72, -2.15), and alanine aminotransferase (WMD: -2.61 IU/L, 95% CI: -4.87, -0.34). Supplementation with melatonin substantially increased serum total antioxidant capacity (WMD: 0.15 mmol/L, 95% CI: 0.08, 0.22) and high-density lipoprotein cholesterol (WMD: 2.04 mg/dL, 95% CI: 0.50, 3.57). No significant effects of melatonin were observed on body weight, waist circumference, body fat percentage, body mass index, fasting insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, triglycerides, diastolic blood pressure, aspartate aminotransferase, or gamma-glutamyl transferase. <b>Conclusions</b>: Melatonin supplementation significantly ameliorated multiple CMRFs.