Melatonin is a physiological indoleamine secreted from the pineal gland into the bloodstream. This hormone has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. Therefore, we assessed the impact of melatonin supplementation on systolic BP (SBP) and diastolic BP (DBP) through a systematic review and meta—analysis of available randomized controlled trials (RCTs). Medline, Scopus, Web of Science, Cochrane library, and Google scholar (until May 2018) were searched to identify potential RCTs with information on melatonin supplementation and BP. Mean Differences (MD) were pooled using a random-effects model. Standard methods were used for assessment of heterogeneity, sensitivity analysis, and publication bias. Pooling 5 RCTs (6 treatment arms) together identified significant reduction for SBP (MD: −3.43 mmHg, 95% confidence interval (CI): −5.76 to −1.09, p=0.004) and DBP (MD: −3.33 mmHg, 95% CI: −4.57 to −2.08, p<0.001) after supplementation with melatonin compared with control treatment. The sensitivity analysis indicated that the results were robust. We did not observe any evidence regarding publication bias. The findings of this meta-analysis support the overall favorable effect of melatonin supplementation on BP regulation.