Objective: Diabetes mellitus is a serious, complex metabolic disorder and growing health threat disease in the world. Berberine, one of the main constituent in Rhizoma coptidis is widely used in the treatment of diabetes. Potential of berberine in the management of diabetic complications, namely diabetic nephropathy and cardiomyopathy, is however, not yet explored. The present study was, therefore, undertaken to explore the potential of berberine for the management of diabetic nephropathy and diabetic cardiomyopathy in high-fat diet (HFD) and low dose streptozotocin (STZ) induced diabetes in rats. Methods: Rats were fed a high-fat diet for 4 w followed by a single intraperitoneal dose of streptozotocin (35 mg/kg). Animals were divided in five groups. Berberine was given orally in two different dose levels (75 mg/kg and 150 mg/kg) for 28 d. Metformin (100 mg/kg) was used as a standard antidiabetic drug. At the end of the study, parameters evaluated includes glycemic profile, lipid profile, left ventricular indices, urinary protein, serum creatinine, blood urea nitrogen and cardiac antioxidants. Histopathology of kidney and pancreas was carried out. Results: Berberine treated groups showed a significant decrease in fasting blood glucose, glycosylated Hb, creatinine, blood urea nitrogen and urinary total proteins, whereas there was a significant improvement in serum insulin, liver glycogen, skeletal muscle glycogen and cardiac antioxidant enzymes. Conclusion: Present study indicated that berberine shows a protective role in diabetes-associated renal and cardiovascular complications.