This study aimed to investigate the effect of ultrasound-assisted extraction under vacuum on bioactive properties of peel and flesh of pitaya fruit, and also compare with sonication under atmosphere condition using the principal component analysis (PCA). Vacuum sonication exhibited better results for total phenolic (56.78–71.54 mg GAE per 100 g for peel; 11.03–17.92 mg GAE per 100 g for flesh) and total flavonoid (95.33–115.71 mg QE per 100 g for peel; 13.26–19.36 mg QE per 100 g for flesh) amounts. DPPH free radical scavenging activity values of peel and flesh increased from 1.97 to 2.53 mmol TE kg-1; from 0.33 to 0.50 mmol TE kg-1 after sonication process, respectively. The main phenolic compounds of pitaya were identified as catechin (1.15–20.31 mg per 100 g) and rutin (0.88–14.55 mg per 100 g) in peel; catechin (1.11–9.35 mg per 100 g) and 3,4-dihydroxybenzoic acid (1.29–3.60 mg per 100 g) in flesh. The combination of vacuum and ultrasound process can be used as a green extraction technology in order to enhance the amounts of bioactive compounds of pitaya fruit.