Abstract: To optimize the extraction process of polysaccharide form Solanum lyratum and investigate its in vitro antioxidative activity. In this study, response surface methodology was employed to optimize the ultrasonic-assisted extraction process of polysaccharides from Solanum lyratum. Single-factor experiments were conducted to explore the effects of three factors: Extraction temperature, extraction time, and solid-liquid ratio on the yield. Fourier transform infrared spectroscopy (FTIR) was used to analyze the structure of Solanum lyratum polysaccharide, and in vitro antioxidant activity was investigated. The results showed that the optimal extraction conditions were the material-liquid ratio of 1:57 g/mL, the extraction time of 58 min, and the extraction temperature of 65 ℃. Under these conditions, the yield of polysaccharides was 7.54%±0.12%. Fourier transform infrared spectroscopy of the extracted polysaccharides exhibited a typical polysaccharide absorbance. Moreover, the half-maximal inhibitory concentrations (IC₅₀) of polysaccharides against DPPH and ABTS⁺ free radicals were 1.104 and 1.408 mg/mL, respectively, indicating significant in vitro antioxidant activity. The results of this study provided a theoretical foundation for the further development and utilization of Solanum lyratum polysaccharides.