Background:The decoction of red dragon fruit peel contains chemical components with antioxidant activity of lowering blood LDL cholesterol levels. Objective: This research aimed to evaluate the antihypercholesterolemic power of red dragon fruit peel ethanolic extract. Materials and Methods: A total of 24 mice were divided into four treatment groups, each receiving distilled water at dose 0.39 ml/20 g body weight (A), red dragon fruit peel extract at dose 5.40 mg/20 g body weight (B) and 10.80 mg/20 g body weight (C), also simvastatin at dose 0.026 mg/20 g body weight (D). All experimental animals were given high fat intake in cow brain suspension for 60 days to increase LDL cholesterol levels in the blood. For 14 consecutive days, hypercholesterolemic mice were given test preparations. Mice were sacrificed on day 75 for blood and aortic samples. Results: The average blood LDL cholesterol levels in mice were 91.67 mg/dl, 63.23 mg/dl, 43.52 mg/dl, and 32.94 mg/dl (p<0.05%). Meanwhile, the average aortic score was 1.09, 0.79, 0.76, and 0.91 in the groups A, B, C and D, respectively. Conclusion: Red dragon fruit peel extract at a dose of 5.4 mg/20 g and 10.8 mg/20 g body weight reduces blood LDL cholesterol levels and the risk of atherosclerosis.