This study was carried out to evaluate the total phenolic content and anti-oxidant activity of methanolic extract of red pitaya, and hypocholesterolemic effect of red pitaya (Hylocereus sp.) on lipid profiles status on hypercholesterolemia induced rats. From the analysis, total phenolic content in red pitaya is 46.06 ± 1.77 mg GAE/100 g fresh weight and antioxidant activity is 76.10% using FTC method. TBA analysis also showed red pitaya extract had high antioxidant effect (72.90%). An in-vivo study also showed red pitaya has hypocholesterolemic effect on induced hypercholesterolemia rats. After 11 weeks of study, total blood cholesterol significant decrease (p