Objective: The current study was performed to evaluate the effects of synbiotic administration on metabolic profiles in overweight diabetic patients with coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was done among 60 diabetic patients with CHD. Participants were randomly divided into 2 groups: group A (n=30) received synbiotic supplements containing 3 probiotic bacteria spices Lactobacillus acidophilus 2×109, Lactobacillus casei 2×109, Bifidobacterium bifidum 2×109 CFU/g plus 800 mg inulin and group B (n=30) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after 12-week intervention to determine metabolic profiles. Results: After 12 weeks of intervention, patients who consumed synbiotic capsule had significantly decreased fasting plasma glucose (- 19.6±74.6 vs.+19.2±66.9 mg/dL, P=0.03), serum insulin concentrations (- 0.7±5.1 vs.+3.3±6.3 µIU/mL, P=0.01), the homeostasis model of assessment-estimated b cell function (- 3.4±19.5 vs.+11.5±21.0, P=0.006) and increased the quantitative insulin sensitivity check index (+ 0.002±0.01 vs.-0.01±0.02, P=0.03) compared with the placebo. In addition, changes in HLDL-cholesterol levels (+ 1.8±5.7 vs.-2.2±6.0 mg/dL, P=0.01) in supplemented patients were significantly different from those of patients in the placebo group. Conclusion: Synbiotic supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on markers of insulin metabolism and HDL-cholesterol levels.