Pomelo fruitlet is a side-product of pomelo, and this study aimed to extract the antioxidative flavonoid compounds from pomelo fruitlets with high efficiency through ultrasonic-associated microwave methods. Scanning electron microscopy analysis indicated that the spatial structure of the pomelo fruitlet powder was changed; microwaves and ultrasonic waves facilitated the formation of globular and curved surfaces, respectively. Ultrasonic-microwave synergistic pretreatment resulted in significantly higher yield. Each type of flavonoid compound was characterized using PR-LCMS analysis, and naringin with high nutritive value was detected in all groups. After purifying the flavone fractions with AB-8 macroporous resin, naringin, 2′′-O-acetyl-3′-O-methylrutin, and 5,7,8,3′-tetrahydroxy-3,4′-dimethoxy were identified, which could act as free radical scavengers to protect erythrocytes from AAPH-induced hemolysis. This study strongly improved the effects of ultrasonic-microwave synergetic methods on the high utilization of pomelo fruitlets, especially in terms of flavonoid extraction and bioavailability.