Abstract: Utilizing lily sourced from Pingliang, Gansu Province as the raw material, ultrasonic, microwave, and ultrasonic combined with microwave extraction approaches were employed to extract polysaccharides from lily. A single-factor test was conducted to investigate the impact of extraction conditions on the polysaccharide content and to compare the polysaccharide content among different extraction methods. The orthogonal experiment method and response surface method were utilized to optimize the extraction process. The results indicated that the ultrasonic combined with microwave extraction method yielded a higher polysaccharide content, with an extraction rate of 19.37%. Microwave power and ultrasonic power were the primary factors influencing the extraction rate of polysaccharide. With the extraction rate of polysaccharide as the response value, the optimized extraction process was as follows: when the microwave power was 600 W, the microwave irradiation time was 25 min, the microwave irradiation temperature was 55 °C, the ultrasonic power was 480 W, the ultrasonic time was 45 min, and the solid-liquid ratio was 1∶25 g/mL, the yield of lily polysaccharide was 23.94%, which was not significantly different from the predicted value (25.03%). Compared to other extraction methods, this approach has a high extraction rate, simple operation, and research value.