Hypercholesterolemia is the leading cause for the development of various diseases made pharmaceutical companies to turn towards the herbal products with fewer side effects. In the present research, the hypocholesterolemic activity of Enicostemma axillare (EA) along with their phytochemical evaluation has been done. Preliminary phytochemical analysis was carried out in different extracts of EA. The hypocholesterolemic effect of 85 % methanolic extract of EA was evaluated in fructose induced hyperlipidemic animals. Antioxidant enzymes such as catalase, TBARS, GSH, GST and lipid profile such as cholesterol, LDL, VLDL, HDL and Triglycerides were analyzed in heart and plasma samples. Administration of EA decreases the lipid profile and TBARS significantly (p<0.05). Likewise, EA administration increases the antioxidant and HDL significantly (p<0.05). The results reveal that EA is a rich source for phytoconstituents and can be used as a potent hypocholesterolemic and antioxidant agent in pharmaceutical industry.