The study validated the antidyslipidemic, antioxidant, and antihyperglycemic effects of Lagenaria siceraria fruit extract in human subjects with dyslipidemia along with subjects of normal health. A total of 200 mL of freshly prepared Lagenaria siceraria fruit extract was administered daily on empty stomach for 90 days. Significant reductions (P < .01) were found in triglycerides and total cholesterol levels in blood. Cardiac risk ratio, atherogenic coefficient, and atherogenicity index of plasma were also improved. Appreciable reductions in body mass index (P < .01) and blood pressure (systolic P < .01, diastolic P < .05) along with a significant reduction (P < .05) in fasting blood glucose levels were also observed in these subjects. Lagenaria siceraria fruit extract exhibited significant antioxidant activity in dyslipidemic subjects as evident from elevations in SOD (P < .05) and GSH levels (P < .01) with marked improvement in catalase (P < .01) and TBARS levels (P < .05). Phytochemical screening confirmed the presence of saponins, glycosides, flavonoids, terpenoids, and phenolic compounds. Lagenaria siceraria fruit extract serves as dietary adjunct in treatment of human dyslipidemia and cardiovascular disease.