Trichosanthes dioica fruit pericarp has a powerful hypolipidemic and antioxidant properties. Wistar rats were divided into five groups (n = 30). The normal control group received vehicle and standard diet throughout the experimental period. Groups II, III, IV, and V were given a high-fat diet and free access of water for 21 days. Experimental groups IV and V were given high-fat diet along with T. dioica extract 400 and 800 mg/kg, respectively. Blood was collected at 21 days, and lipid profile estimation was performed. The phytochemical screening was performed by different phytochemical screening methods. Lipid peroxidation and catalase activity were done by taking a liver tissue sample. The phytochemical screening of extract showed good results and indicated the presence of phytoconstituents in extract. 2,2-Diphenyl-1-picrylhydrazyl scavenging activity of T. dioica was found to be 65.79% at a concentration of 100 μg/ml extract, whereas that of the control was 94.06%. The Wistar rats fed with a high-fat diet with T. dioica showed a significant decrease in total cholesterol (TC), triglycerides (TG), very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) levels and an increase in high-density lipoprotein (HDL) level. The lipid peroxidation and catalase activity of methanol extract of T. dioica were significantly reduced with individual comparison with all groups. The methanol extract of T. dioica has the hypolipidemic effect, which showed a decrease in TC, TG, VLDL, and LDL levels and an increase in HDL level in Wistar rats. It also has antioxidant properties. In this study, we have evaluated the antioxidant and the antihyperlipidemic activities of T. dioica in high-fat diet induced hyperlipidemia in Wistar rats.