Background:Diabetes mellitus is a prevalent metabolic disorder characterized by reduced insulin activity leading to hyperglycemia, affecting over 425 million people globally. Traditional treatments, including sulfonylureas and biguanides, often have undesirable side effects, prompting a shift toward herbal remedies for diabetes management and prevention. Objective:This study aims to evaluate the antidiabetic effects of budding leaves from Clerodendrum infortunatum compared to metformin in preventing streptozotocin (STZ)-induced hyperglycemia in rats. Materials and Methods:An in vivo study was conducted using adult male Wistar albino rats. STZ was administered on day 15 and was followed till day 18. Methanolic extract of C. infortunatum (MECI) at different dosages (250, 500, and 1000 mg), metformin (500 mg), and normal saline were administered to different groups of rats. Blood glucose levels (at day 1, 15, and 18) and biochemical parameters (lipid profile, hepatic and renal parameters, and oxidative stress markers) were measured at days 1 and 18. At the end, a histopathological examination of the pancreas, liver, and kidney was done. Statistical analyses were performed to determine significance. Results:The study found that while the MECI at 500 mg/kg showed a significant reduction in blood glucose levels compared to the diabetic control group (P < 0.0001), it was less effective than metformin (P > 0.05). Higher doses of MECI demonstrated potential in improving liver and renal parameters (P < 0.0001), as well as reducing oxidative stress (P < 0.0001) compared to metformin indicating its beneficial effects in diabetic conditions. Conclusion:C. infortunatum shows promise as an adjunctive therapy for the prevention of diabetes due to its multifaceted mechanisms, including enhancing insulin secretion and reducing oxidative stress. However, further clinical trials are needed to confirm these findings and establish optimal dosages.