ABSTRACT: BACKGROUND:Hylocereus polyrhizus and Hylocereus undatus are two varieties of the commonly called pitaya fruits, and pitaya fruits have gained popularity in many countries all over the world. However, studies on chemical composition and the nutritional quality of pitaya flesh peel are limited. RESULTS:Extracts of pitaya (H. polyrhizus and H. undatus) peel were extracted by supercritical carbon dioxide extraction, and analyzed by gas chromatography-mass spectrometry analysis. Their cytotoxic and antioxidant activities were investigated. The main components of H. polyrhizus extract were β-amyrin (15.87%), α-amyrin (13.90%), octacosane (12.2%), γ-sitosterol (9.35%), octadecane (6.27%), 1-tetracosanol (5.19%), stigmast-4-en-3-one (4.65%), and campesterol (4.16%), whereas H. undatus were β-amyrin (23.39%), γ-sitosterol (19.32%), and octadecane (9.25%), heptacosane (5.52%), campesterol (5.27%), nonacosane (5.02%), and trichloroacetic acid, hexadecyl ester (5.21%). Both of the two extracts possessed good cytotoxic activities against PC3, Bcap-37, and MGC-803 cells (IC50 values ranging from 0.61 to 0.73 mg/mL), and the activities of their main components were also studied. Furthermore, these extracts also presented some radical scavenging activities, with IC50 values of 0.83 and 0.91 mg/mL, respectively. CONCLUSION:This paper provides evidence for studying the chemical composition of supercritical carbon dioxide extracts of pitaya peel and their biological activity.