The Box-Behnken design combined with response surface method was employed to optimize ultrasonic-assisted extraction of flavonoids from Taraxacum officinale. The optimized results showed that the highest extraction yield with ultrasonic-assisted extraction could reach 2.62% using 39.6% (v/v) ethanol and 59.5 : 1 (mL/g) liquid-solid ratio for 43.8 min. The crude extract was then purified by HPD-100 macroporous adsorption resin, and the flavonoids content in the purified extract increased to 54.7%. The antioxidant activity of the purified flavonoids was evaluated in vitro by scavenging capacity of ABTS or DPPH, β-carotene bleaching, and FTC test. The knowledge obtained from this study should be useful to further develop and apply this plant resource.