¹Molecular Medicine, Nutrigenomics and Public Health Research Laboratory, Department of Bio-Medical Laboratory Science and Management, Vidyasagar University, India DOI : 10.29228/jrp.2022.00 Diabetes mellitus needs efficient therapeutic strategies with nominal undesirable effects. This comparative dose-dependent study aimed to search out the hyperglycemic and oxidative stress corrective efficacies of hydromethanol (60:40) extract of root tuber of Ipomoea mauritiana (Jacq.) (IMHME) in streptozotocin (STZ)-induced diabetic male rats. The in-vivo study has been designed to identify the most potent dose for such therapeutic outcomes. Single dose of STZ (4 mg/100 g body weight (BW)) was administered intramuscularly in rats to induce diabetes. Subsequently, rats were allowed for treatment at doses of 5, 10, 20, and 30 mg per 100 g BW of the IMHME for 4 weeks. Blood glucose level in fasting, insulin level, and activities of glucose-6-phosphatase, hexokinase, catalase, and superoxide dismutase were assessed to interpret the hypoglycemic and anti-oxidative properties of IMHME. The IMHME demonstrated a dose-dependent increase in insulin level with a concomitant decrease in fasting blood glucose level and rectification of said enzyme activities. Additionally, IMHME revealed potent anti-oxidative effects, as evidenced by a significant correction in oxidative metabolic biomarkers, i.e., thiobarbituric acid reactive substances, along with increase in pancreatic islet diameter. The outcome of this comparative dose-dependent investigation focused on the 10 mg dose of IMHME, which has the optimal therapeutic efficacy in improving diabetes by mitigating oxidative stress. No significant difference was noted among the groups under the treatment of 10, 20, and 30 mg doses. The promising results form the basis for exploration of the underlying mechanism and the translation of this into clinical research. Keywords : Ipomoea mauritiana (Jacq.); Anti-diabetic; Oxidative stress; Hexokinase; Pancreatic islet