This study aims to optimize the ultrasonic-assisted deep eutectic solvent(DES ) extraction process of total flavonoids from Broussonetia papyrifera leaves (TFBPL) and evaluate its antioxidant activity.Based on the single factor experiments,the extraction process was optimized by response surface methodology.The antioxidant activity was evaluated by determining the scavenging capacity of TFBPL against DPPH,ABTS and hydroxyl radicals in vitro.The results revealed that when betaine-ethanol was employed as the DES at a molar ratio of 1∶3,water content of 29.0% (V/V),solid-liquid ratio of 1∶43 (g/mL),and ultrasonic time of 32 min,the yield of TFBPL reached 60.66±0.46 mg/g.Under the same conditions,the yield of TFBPL obtained by this method was 1.8-3.2 times higher than that obtained by traditional solvent extraction.Within a mass concentration range of 0.5 to 60 mg/g,the scavenging rates of TFBPL against DPPH,ABTS and hydroxyl radicals were 72.97%±0.98%,98.53%±0.56% and 51.60%±0.82%,respectively.Therefore,the ultrasonic-assisted DES extraction process for TFBPL is both efficient and environmentally friendly,and the extracted total flavonoids exhibit significant antioxidant activity in vitro.