The pitaya peel powder was mixed with 50% ethanol solution at a ratio of 1:10 (w/v) for 24 h to obtain the pitaya peel ethanol extract (E). The extract was further fractionated with supercritical carbon dioxide (SC–CO2) under the operating conditions: temperature 40 °C and pressure of 30, 25, 20 or 10 MPa into R, F1, F2 or F3 fractions, respectively. Our results confirmed SC-CO2 fractionation significantly influenced the distribution of phenolic compounds, polysaccharides and betalains in fractions and thus affected their physico-chemical properties. Bioactive compounds majorly distributed in F1; consequently, DPPH and ABTS radicals scavenging activities of F1 are higher than those of other fractions. The IC50 values of DPPH and ABTS scavenging ability were 0.78 mg/mL and 0.69 mg/mL for F1 fraction, respectively. Linear structure model analysis showed that the scavenging activities of the both free radicals were positively related to phenolic compounds and polysaccharide components. The strong red-orange color spectrum of E was simultaneously fractionated into the red-orange color F1, the bright red color of F2 and F3 and the vivid orange color of R.