Hyperlipidemia is a condition of lipid such as cholesterol and triglycerides in the blood are high, which is the cause of other diseases. This condition also causes an increase in free radicals resulting in oxidative stress. Purple sweet potato leaves and red yeast rice have been reported to have antihyperlipidemic and antioxidant activity in several studies. This study aimed to examine the effect of the combination of purple sweet potato leaves extract and red yeast rice on cholesterol and triglyceride levels as well as MDA levels and GPx activity on rats induced by a high-fat diet. Experimental animals were randomly divided into 6 groups of 5 mice each: group 1 being the normal group; group 2 positive control; group 3 negative control; group 4 purple sweet potato leaf extract 400 mg/kg BW; group 5 red yeast rice 40 mg/kg BW; group 6 combination of purple sweet potato leaf extract 360 mg/kg BW and red yeast rice 40 mg/kg BW. Rats were treated with high-fat feed for 28 days, on day 15-28 were given oral preparations. At the end of the study, all rats were blood drawn to measure cholesterol and triglyceride levels, then rats were sacrificed and the liver was taken to measure MDA and glutathione peroxidase levels. The administration of purple sweet potato leaf extract, red yeast rice, and their combination significantly (p<0,05) reduced cholesterol, triglyceride, and MDA levels, and increased GPx activity, with the best effect in the combination group. This finding showed that the combination of purple sweet potato leaf extract and red yeast rice had antihyperlipidemic and antioxidant activity in hypercholesterol rats.