Introduction: We have previously demonstrated that sequentially extracted methanolic fractions of Boerhaavia diffusa (Linn.) showed marked antioxidant, antidiabetic and oxidative-DNA damage protective properties in vitro. The present study was undertaken to evaluate the beneficial effects of B.diffusa (Linn.) methanolic root extract and its partially purified bioactive fraction on streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Methods: The diabetic rats were treated for fourteen weeks either with methanolic extract of B. diffusa root (D-MT1, D-MT2, and D-MT3 : doses of 50, 150, and 300 mg/rat/day, respectively), partially isolated bioactive fraction (DBT: 0.5 mg/rat/day), or glibenclamide (D-GT: 0.5 mg/rat/day). Results: The level of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were significantly alleviated in D-MT- and D-BT treated groups after fourteen weeks of administration. Moreover, plasma lipid profile, free fatty acids (FFAs), phospholipids (PLs), HMG-CoA reductase (HMG-R) activity, conjugated diene (CD), lipid hydroperoxide (LOOH), and malondialdehyde (MDA) were also markedly ameliorate d in all treatment groups. In addition, the activity of antioxidant enzymes, e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (Gred), and glutathione-S-transferase (GST), were also significantly restored by D-MT — and D-BT — treated groups. Furthermore, histologically, all the unseemly features of nephropathy were extensively regressed and normalized by the administration of B. diffusa and its bioactive fraction. Conclusions: Our results demonstrate a strong antidiabetic and hypolipidemic impact of B. diffusa extract an ideal alternative therapeutic agent in the prevention and treatment of diabetes as well as diabetes-linked hyperlipidemia.