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 in 56 patients with T2DM and CHD. Patients were randomly divided into two groups to receive either 500 mg resveratrol/day (n=28) or placebo (n=28) for 4 weeks. Resveratrol reduced fasting glucose (β -10.04 mg/dL; 95% CI, -18.23, -1.86; P=0.01), insulin (β -1.09 µIU/mL; 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; 95% CI, 1.72, 5.05; P<0.001) and significantly decreased 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; 95% CI, 17.33, 100.44; P=0.006) and a significant reduction in malondialdehyde (MDA) levels (β -0.21 µmol/L; 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 peripheral blood mononuclear cell (PBMC) of T2DM patients with CHD. Resveratrol supplementation did not have any effect on inflammatory markers. 4-week supplementation with resveratrol in patients with T2DM and CHD had beneficial effects on glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, TAC and MDA levels. Resveratrol also upregulated PPAR-γ and SIRT1 in PBMC of T2DM patients with CHD.