The red pitaya, rich in micronutrients, has recently generated a great deal of consumer interest, therefore, this paper was designed to study the total phenolic content, antioxidant activity and antiproliferative activity of red pitaya on melanoma cells and to determine if it is a valuable source of antioxidants and an anticancer agent. The total phenolic contents of flesh (42.4 ± 0.04 mg of gallic acid equivalents (GAE)/100 g of flesh fresh weight) and peel (39.7 ± 5.39 mg of GAE/100 g of peel fresh weight) were similar. The flavonoid contents of flesh and peel did not vary much (7.21 ± 0.02 mg vs. 8.33 ± 0.11 mg of catechin equivalents/100 g of flesh and peel matters). The concentrations of betacyanins expressed as betanin equivalents per 100 g of fresh flesh and peel were 10.3 ± 0.22 and 13.8 ± 0.85 mg, respectively. The antioxidant activity, measured by the DPPHradical dot method at EC50, was 22.4 ± 0.29 and 118 ± 4.12 μmol vitamin C equivalents/g of flesh and peel dried extract; the values of EC50, determined by the ABTSradical dot+ approach, were 28.3 ± 0.83 and 175 ± 15.7 μmol of trolox equivalents antioxidant capacity (TEAC)/g of flesh and peel dried extract, respectively. The antiproliferative study on B16F10 melanoma cells revealed that the peel (EC50 25.0 μg of peel matter) component was a stronger inhibitor of the growth of B16F10 melanoma cancer cells than the flesh. The results indicated that the flesh and peel were both rich in polyphenols and were good sources of antioxidants. The red pitaya peel fulfilled its promise to inhibit the growth of melanoma cells.