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In order to determine the effect of ultrasonic extraction on the content and functional activity of collagen peptide from Tibetan sheep skin, solid-liquid ratio, ultrasonic power and ultrasonic time were studied by response surface method to determine the best ultrasonic extraction process of collagen peptide. The antioxidant capacity, reduction power and ·OH scavenging ability of collagen peptide from Tibetan sheep skin was analyzed. The results showed that ultrasound-assisted treatment had significantly affected the content of collagen peptide and antioxidant activity. The optimal ultrasonic extraction conditions were solid-liquid ratio 1:18, ultrasonic power 220 W and ultrasonic time 27 min. The collagen peptide content of Tibetan sheep skin was 30.21%±1.67%. The reduction power and ·OH scavenging rate of collagen peptide after ultrasonic assisted extraction were 0.49 and 83.2%, which were increased by 4% and 38.3% compared with those before ultrasonic extraction, respectively. After gastrointestinal digestion, the reduction power and ·OH decreased to a certain extent, but still had good antioxidant activity. Ultrasound-assisted extraction of collagen peptide from Tibetan sheep skin has the advantages of increasing the content of collagen peptide and enhancing antioxidant activity in vivo, which provides data reference for the development of functional products.