Abstract: The objective of the present study was to evaluate the antidiabetic activity of methanol extract of aerial parts of Cucurbita maxima (MECM) for its purported use in diabetes. Antidiabetic activity of MECM was evaluated in Wistar albino rats against streptozotocin (50 mg kg-1, i.p.,) at the doses of 200 and 400 mg kg-1, p.o. for 14 days. Glibenclamide (500 μg kg-1) was used as reference drug. Fasting blood glucose (FBG) levels were measured on day 0, 4, 8 and 15. Antioxidant activity of the extract was determined by measuring lipid peroxide, catalase and glutathione (reduced) levels of liver, kidney and pancreas. In addition, biochemical parameters (SGPT, SGOT, ALP) were estimated. Histological study of liver, kidney and pancreas was also performed. FBG levels were reduced in a treatment-duration dependant manner and 60.88, 67.79 and 64.30% reduction with respect to the initial levels were observed on 15th day with low and high dose of MECM and glibenclamide, respectively. The changes in antioxidant and biochemical parameters observed with diabetic control group were reversed towards normal levels with extract and standard treated groups. Histological observations showed good correlations with other results. The results explored potent antidiabetic activity of the methanol extract of C. maxima aerial parts.