Background: Diabetes is a serious global health issue and increases the risk of several chronic diseases. However, if hyperglycemia and other metabolic abnormalities related to diabetes are controlled, fewer micro- and macrovascular complications may occur. Objective: To investigate whether daily supplementation with berberine in combination with cinnamon could have effect on cardiometabolic risk factors, such as impaired glucose regulation, dyslipidemia, and hypertension in patients with diabetes. Methods: Patients with type 2 diabetes were recruited to participate in a parallel, double-blind, placebo-controlled, randomized study. Participants were randomized into berberine in combination with cinnamon supplementation or placebo group. Participants were then asked to take a divided daily dose of berberine and cinnamon or placebo for 12 weeks. ANCOVA was then performed to evaluate the differences between the two groups, controlling for the respective baseline values. Results: At the end of study, fasting blood sugar (FBS) (P = 0.031) and hemoglobin A1C (HbA1c) (P = 0.013) were significantly lower in participants taking berberine plus cinnamon than those taking the placebo capsules. The results of the serum lipid profile also indicated a significant difference in the level of low density lipoprotein cholesterol (LDL-C) (P = 0.039), while no difference was observed in the levels of total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides between the study groups. In addition, there was no difference in other measured metabolic and anthropometric parameters between the two groups. Conclusion: Twelve weeks of berberine plus cinnamon consumption reduced blood FBS, HbA1c and LDL-C concentration in patients with diabetes.