BACKGROUND & AIMS: Diabetes mellitus is a metabolic disorder, in which chronic systemic inflammation and oxidative stress contribute to the progression of this condition and its complications. Melatonin, a hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This review aims to evaluate the effects of melatonin supplementation on markers of oxidative stress and inflammation in diabetic patients. METHODS: A thorough literature search of databases, including PubMed, Embase, Web of Science, Cochrane Central, CNKI, and Scopus, was conducted through October 2023. We included randomized controlled trials investigating the effects of melatonin on markers of inflammation and oxidative stress, compared to placebo in patients with diabetes. The data was analyzed using the random-effects model and the summary effect size was determined using the standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Fourteen studies with 823 participants were included. Our analysis indicates that melatonin can lead to significant reductions in levels of C-reactive protein (CRP) [SMD = -0.75; 95% CI: -1.37, -0.12; P = 0.018], tumor necrosis factor-alpha (TNF-α) [SMD = -0.40; 95% CI: -0.64, -0.15; P = 0.001], interleukin (IL)-1 [SMD = -0.75; 95% CI: -1.03, -0.47; P < 0.0001], IL-6 [SMD = -0.79; 95% CI: -1.07, -0.51; P < 0.0001], and malondialdehyde (MDA) [SMD = -0.61; 95% CI: -0.80, -0.43; P < 0.0001]. Furthermore, we found a significant increase in levels of total antioxidant capacity (TAC) [SMD = 0.81; 95% CI: 0.12, 1.51; P = 0.021], glutathione (GSH) [SMD = 0.66; 95% CI: 0.28, 1.03; P = 0.001], and superoxide dismutase (SOD) [SMD = 1.69; 95% CI: 0.80, 2.58; P < 0.0001] following melatonin consumption in patients with diabetes. CONCLUSION: Melatonin supplementation is a promising complementary strategy to attenuate oxidative stress and inflammation in diabetic patients.