Diabetes mellitus is a complex disorder that disturbs the metabolism of carbohydrates, fats, and proteins. Medicinal plants play an important role in the management of diabetes mellitus. The present study was aimed to evaluate the antidiabetic potential of Zaleya decandra roots on alloxan-induced diabetes in rats. Oral administration of ethanolic extract of the root (200 mg/kg body weight/day) for 15 days restored the levels of glucose, cholesterol, triglycerides, total proteins, urea, creatinine, lipid peroxidation level, and antioxidant enzymes significantly in diabetic rats. Histopathological studies showed significant changes like necrosis and degeneration in the liver and pancreas of alloxan-induced diabetic rats. Also these histopathological abnormalities were found to be normalized after treatment with Z. decandra extract. The efficacy of the root extract was found to be equivalent when compared to the standard hypoglycemic drug glibenclamide (1.25 mg/kg body weight/day, orally) in diabetic rats.