Hypercholesterolemia is a condition by an increase total cholesterol and Low Density Lipoprotein (LDL) cholesterol levels, which can lead the secretion of proinflammatory cytokines Interleukin-6 (IL-6) through the activation of the NF-kB pathway oxidative stress, and increase in Malondialdehyde (MDA) levels. Studies showed that the extract of bitter melon contains flavonoids as antioxidants can reduce cholesterol levels. To find out the effect of bitter melon extract on total cholesterol levels, IL-6, and MDA in hypercholesterolemic rats. Experimental research with Post Test Only Group Design. The research subjects were 25 wistar rats divided into 5 groups. Group K(N) normal rats, K(-) were only given a hypercholesterol diet for 28 days, groups K(+), P1, and P2 were given a hypercholesterol diet for 14 days followed by 14 days of hypercholesterol diet along with simvastatin at 0.09 mg/kgBW, bitter melon extract at 150 mg/kgBW, and combination of bitter melon extract at 75 mg/kgBW and simvastatin at 0.045 mg/kgBW. On the 29th day the rats were examined. The results of the Shapiro-Wilk and Levene tests showed that the data were normally distributed and homogenous. One-Way ANOVA and Tukey test was found that the levels of cholesterol, IL-6, and MDA in the P1, P2, and P3 hypercholesterolemic rat groups underwent significantly (p0.05) compared to the control group. The extract of bitter melon, simvastatin, and the combination of simvastatin and bitter melon extract have effect on reducing cholesterol levels, IL-6, and MDA in hypercholesterolemic rats.