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Objective: The objective was to determine the effects of resveratrol supplementation on glucose homeostasis, oxidative stress, inflammation and microRNAs expression in patients with diabetes mellitus type 2 on oral hypoglycemic drugs. Method: This was a randomized, double blinded placebo-controlled parallel group trial. The diabetic patients (n = 110) were randomly assigned either to resveratrol (n = 55) and placebo (55) groups after informed consent and given once daily resveratrol 200 mg and cellulose capsules respectively for 24 weeks. Fasting glucose, insulin, HbA1c, lipid profile, TNF- α, IL-6, hs-CRP, MDA & circulatory microRNAs were measured at start and end of 24- week intervention. Results: Out of 110 patients recruited, 94 patients completed the study comprising of 45 in resveratrol and 46 in placebo group. The resveratrol supplementation after 24 weeks was resulted in significant reduction [mean difference (95%CI)] of plasma glucose[− 0.50(−0.94 to −0.06)], insulin[− 1.31(−2.24 to −0.38)], homeostatic model assessment of insulin resistance[− 0.83(−1.37 to −0.29)], malondialdehyde[− 0.36(−0.61 to −0.11)], high sensitive-C-reactive protein[− 0.35(−0.70 to −0.01)], tumor necrosis factor-alpha[− 1.25(−1.90 to −0.61)] and interleukin-6[− 1.99(−3.29 to −0.69)]. More than two-fold down regulation in miRNA-34a, miRNA-375, miRNA-21, miRNA-192 and up regulation in miRNA-126 and miRNA-132 expression was noted in patients receiving resveratrol as compared to placebo. No side effects were reported during the trial. Conclusion: Resveratrol supplementation contributes in improvement of glycemic control by reducing insulin resistance. It has significant beneficial impact on chronic inflammation, oxidative stress and associated microRNA expression in diabetic patients. Thus, supplementation of resveratrol along with oral hypoglycemic agents may be useful in the reduction of diabetic associated complications.