This study was performed to investigate the effects of resveratrol on metabolic status in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was performed with 56 patients having T2DM and CHD. The patients were randomly divided into two groups to receive either 500 mg resveratrol per day (n = 28) or placebo (n = 28) for 4 weeks. Resveratrol reduced fasting glucose (β-10.04 mg dL-1; 95% CI, -18.23, -1.86; P = 0.01), insulin (β-1.09 μIU mL-1; 95% CI, -1.93, -0.24; P = 0.01) and insulin resistance (β-0.48; 95% CI, -0.76, -0.21; P = 0.001) and significantly increased insulin sensitivity (β 0.006; 95% CI, 0.001, 0.01; P = 0.02) when compared with the placebo. Resveratrol also significantly increased HDL-cholesterol levels (β 3.38 mg dL-1; 95% CI, 1.72, 5.05; P < 0.001) and significantly decreased the total-/HDL-cholesterol ratio (β-0.36; 95% CI, -0.59, -0.13; P = 0.002) when compared with the placebo. Additionally, resveratrol caused a significant increase in total antioxidant capacity (TAC) (β 58.88 mmol L-1; 95% CI, 17.33, 100.44; P = 0.006) and a significant reduction in malondialdehyde (MDA) levels (β-0.21 μmol L-1; 95% CI, -0.41, -0.005; P = 0.04) when compared with the placebo. Resveratrol upregulated PPAR-γ (P = 0.01) and sirtuin 1 (SIRT1) (P = 0.01) in the peripheral blood mononuclear cells (PBMCs) of T2DM patients with CHD. Resveratrol supplementation did not have any effect on inflammatory markers. Four-week supplementation of resveratrol in patients with T2DM and CHD had beneficial effects on glycemic control, HDL-cholesterol levels, the total-/HDL-cholesterol ratio, TAC and MDA levels. Resveratrol also upregulated PPAR-γ and SIRT1 in the PBMCs of T2DM patients with CHD.