ABSTRACT Hyperlipidemia is a major factor that can promote atherosclerosis and atherosclerosis-related conditions. Cardiovascular disease (CVD) is the epidemic of modern civilization in which hyperlipidemia contributes significantly to its pathogenesis. This study aimed to investigate the antihyperlipidemic property of Antigonon leptopus leaves using the methanolic crude extract (ALME) in Triton-X-100 induced hyperlipidemic male Sprague-Dawley rats during seven-day treatment period. The efficacy of ALME 100, 200, 400mg/kg was compared to the standard simvastatin (10 mg/kg, p.o.) in Triton X-100-induced hyperlipidemic rats. Effect of ALME on serum lipid profile like Total Cholesterol (TC), Triglycerides (TG), Low-Density Lipoprotein-Cholesterol (LDL-C), Very Low-Density Lipoprotein-Cholesterol (VLDL-C) and High-Density Lipoprotein-Cholesterol (HDL) were estimated. The results demonstrated that the ALME has an antihyperlipidemic potential. Different doses of ALME significantly reduced the TC, TG, LDL-C, and VLDL-C in Triton X-100-induced hyperlipidemic rats (pvalue <0.05). The histopathological evaluation also revealed the positive effect of the plant extract, with ALME 100 mg/kg showing promising tissue-specific antihyperlipidemic effect.