The box-behnken design combined with response surface methodology was used to optimize ultrasonic-assisted extraction of flavonoids from Suaeda salsa (Linn.) Pall. The results indicate that the highest extraction rate of flavonoids by ultrasonic-assisted extraction could arrive 5.17% using 500W ultrasonic power, 69% ethanol as solvent, 77°C extraction temperature, 1:40 solid to liquid ratio for 58 min extraction. The flavonoids-enriched extracts exhibited quite strong reducing property and excellent inhibitions of DPPH radical, hydroxyl radical. Meanwhile, it was found that the bioactivities appeared to be dose-dependent of flavonoids.