Supercritical carbon dioxide (SC-CO(2)) extraction of flavonoids from pomelo (Citrus grandis (L.) Osbeck) peel and their antioxidant activity were investigated. Box-Behnken design combined with response surface methodology was employed to maximize the extraction yield of flavonoids. Correlation analysis of the mathematical-regression model indicated that a quadratic polynomial model could be used to optimize the SC-CO(2) extraction of flavonoids. The optimal conditions for obtaining the highest extraction yield of flavonoids from pomelo peel were a temperature of 80 °C, a pressure of 39 MPa and a static extraction time of 49 min in the presence of 85% ethanol as modifier. Under these conditions, the experimental yield was 2.37%, which matched positively with the value predicted by the model. Furthermore, flavonoids obtained by SC-CO(2) extraction showed a higher scavenging activity on hydroxyl, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals than those obtained by conventional solvent extraction (CSE). Therefore, SC-CO(2) extraction can be considered as a suitable technique for the obtainment of flavonoids from pomelo peel.