Abstract: Objective: To enhance the yield of Sophora flavescens polysaccharides and elucidate their antioxidant and hypolipidemic properties, we optimized the polysaccharide extraction process through orthogonal experiments, followed by in vitro evaluation of their antioxidant and hypolipidemic activities. Methods: Employing polysaccharide yield as the primary metric, we conducted orthogonal experiments to optimize the extraction process, building upon preliminary one-way experiments. We investigated the impact of extraction temperature, number of extractions, material-liquid ratio, and extraction time on the polysaccharide yield of Sophora flavescens. Furthermore, we assessed the in vitro antioxidant activity of the polysaccharides by examining their scavenging potential against DPPH radicals, hydroxyl radicals, and superoxide anion radicals. Additionally, the in vitro hypolipidemic activity of the polysaccharides was evaluated by their binding affinity to sodium cholate (SC), sodium taurocholate (STC), sodium glycylcholate (SGC), and mixed bile salts (MBS). Results: The optimal conditions for the extraction of Sophora flavescens polysaccharide were determined as follows: a temperature of 85 ℃, a material-liquid ratio of 1:35 (g:mL), and an extraction duration of 3.5 hours, yielding an average polysaccharide content of 3.07%±0.07%. The scavenging efficiencies of Sophora flavescens polysaccharides against DPPH radicals, hydroxyl radicals, and superoxide anion radicals at a concentration of 5 mg/mL were measured at 60.1%±3.6%, 39.6%±3.1%, and 45.1%±4.1%, respectively. Furthermore, the binding affinities of Sophora flavescens polysaccharides to SC, STC, SGC, and MBS at a concentration of 10 mg/mL were determined to be 34.4%±0.75%, 45.4%±0.15%, 19.7%±0.94%, and 37.7%±0.64%, respectively. Conclusion: Sophora flavescens polysaccharide exhibits notable in vitro antioxidant and hypolipidemic activities. This investigation furnishes a foundational understanding for the potential development and exploitation of Sophora flavescens polysaccharide.