Background: Diabetes mellitus is one of the most common metabolic diseases in the world. Recently, willingness to use alternative treatments to control and reduce blood sugar levels has noticeably increased. The general objective of this study is to investigate the hypoglycemic effect of the active ingredient of Berberis (Berberine) in patients with type 2 diabetes. Methods: In this double-blind randomized controlled placebo trial, 84 patients with type 2 diabetes were evaluated. The patients were divided in 2 groups (42 each). In addition to their previous drugs, new diet, and life style each group received Berberine capsules 500 mg or placebo twice daily for 4 weeks. At baseline, weight, height, blood pressure, and BMI were calculated for all patients. Fasting plasma glucose, post-meal plasma glucose, fructosamine, lipid profile, fasting blood insulin levels, BUN, creatinine, and liver enzymes were taken from all patients before the study and after 4 weeks. HOMA-IR and HOMA-β% were calculated.