Aims: The objective of this study was to evaluate the hypolipidemic effect, anti-inflammatory and antioxidant properties of Citrullus lanatus seed extract in cholesterol induced experimental obese mice. Methods and Material: Adult male Mus Musculus mice were divided into four groups. The control group (S) was fed with flour balls (100 mg/mice), group (B) was fed with cholesterol (400 mg/kg/day), group (E) was fed with cholesterol (400 mg/kg/day) plus C. lanatus seed extract (120 mg/kg/day) and the group (R) was treated with C. lanatus seed extract (120 mg/kg/day). Cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, AST, ALT and CRP were measured with enzymatic methods. To elucidate the antioxidant property, the enzymatic antioxidants such as glutathione (GSH) and catalase, in hepatic supernatant have been determined. Statistical analysis used: The results were analyzed by ANOVA test and Tukey’s multiple comparison tests (SPSS V.20). Results: The results showed that the administration of seed extract of C. lanatus significantly decreased serum cholesterol, TG and LDL-c levels, and significantly increased serum HDL-c level. Hyperlipidemic diet induced a significant rise in AST and ALT concentrations. The administration of the seed extract of C. lanatus effectively reduced cholesterol. The CRP concentrations were significantly elevated after the administration of cholesterol to mice. The results showed a significantly high decrease in CRP values in the plant group. The glutathione was reduced, and the catalase levels in plant group were significantly decreased. Conclusions: This study demonstrated a good anti-hyperlipidemic, anti-inflammatory and antioxidant potential of C. lanatus, which fitted well with their use in folk medicine.