Papaya (Carica papaya L.) has a diversity of bioactive compounds with recognized antioxidant effects. However, obtaining these compounds presents challenges related to extraction, which must be economical, fast and with high efficiency. In the present study, the performance of microwave irradiation was evaluated to recover extracts with a high content of polyphenols, flavonoids, and an effective antioxidant activity from a mixture of papaya peel and pulp. The factors solid:solvent ratio, microwave power, and ethanol-water mixture were evaluated. The results showed that the maximum content of bioactive compounds was reached after 3 minutes of extraction with the optimum conditions of 340W for power, 23.34% for mixture ethanol:water and 80.60 for solid:solvent ratio. The optimal extract presented a concentration of 1186.39 ± 44.49 mg GAE/100gFW for polyphenols and 43.88 ± 6.94 mg CE/100gFW for flavonoids and antioxidant activity of 3920.48 ± 31.97 mol TE/100gFW, values higher than those reported by other authors. It is confirmed that the application of microwaves in the process of extraction of bioactive compounds reduces time, costs and is efficient to obtain extracts of papaya with an effective antioxidant activity.