AbstractUltrasonic‐assisted extraction is a rapid and effective extraction method that uses ultrasound energy and solvents to extract target compounds from various plant matrices. In this study, the ultrasonic‐assisted extraction conditions of sour jujube were optimized. A five‐level central composite design (CCD) with four variables was used to evaluate ultrasonic treatment variables influencing the total saponin content (TSC), total flavonoid content (TFC), and total phenolic content (TPC) extracted from sour jujube. The solvent concentration, extraction time, ultrasonic power, and solid‐to‐liquid (S/L) ratio were optimized using aqueous ethanol and methanol solutions as extraction solvents. A central composite design (CCD) was used for an in‐depth study, and then the optimal value that could produce the maximum TPC, TFC, TSC, and four in vitro antioxidant activities (scavenging activity of hydroxyl free radicals, ferric‐reducing antioxidant power (FRAP), phosphomolybdic acid reduction method, and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical‐scavenging activity) was determined. Hydrogen peroxide‐induced oxidative stress experiment confirmed that the Jujube extract could have an antioxidant role in vivo. The relationship between the contents of three compounds and the antioxidant activity in vitro and in vivo was further studied. The results showed that optimizing methanol and ethanol extraction process parameters could improve target components’ extraction efficiency. Under the optimum conditions, the TFC and TPC yields of sour jujube by ethanol are better than methanol, while the yield of TSC by methanol is better than ethanol. In vivo data showed that Jujube extract protects against the adverse effects of oxidative stress and improves the life span of female and male Drosophila. This study provides a valuable reference for the full use of Ziziphus jujube, as well as a new direction in food development.