Abstract: To optimize the ultrasonic-assisted extraction process of flavonoids from Ziziphus jujuba Mill var. spinosa leaves(ZSL),the response surface methodology was used and its antioxidant activity was explored. Based on the single factor experiment,the ratio of liquid to material,ethanol concentration,ultrasonic power and ultrasonic time were selected and response surface experiment was designed. The optimal extraction conditions were as follows:Ratio of liquid to material 30.25:1 mL/g,ethanol concentration 79.00%,ultrasonic power 301.00 W,and ultrasonic time 32.00 min. The actual extraction rate of was 4.21%.The relative error was 6.65% compared with the predicted value of 4.51%,which proved that the theoretical predicted value of the model fitted well with the actual value. The half maximal inhibitory concentration(IC₅₀)of the flavonoids to DPPH,ABTS and ·OH radicals were 111.51,23.06 and 253.73 μg/mL,respectively,indicated that it had strong reducing power. The flavonoids from ZSL could effectively enhance the resistance to heat stress and H₂O₂ oxidative stress of Caenorhabditis elegans(C. elegans),inhibited the decrease of GSH-Px and SOD activity in worms caused by oxidative damage,inhibited the increasing of MDA content,and had a good role of the resistance to oxidative damage.