This study investigates the extraction and antifatigue activities of polysaccharides from *Artemisia argyi* leaves (AALPs) using ultrasound-assisted extraction (UAE) and hot water extraction (HWE). The optimal UAE conditions were determined to be 300 W ultrasonication power, 51 °C temperature, a liquid-to-solid ratio of 20 mL/g, and 47 minutes of ultrasonication time, yielding a maximum extraction rate of 10.49%. Compared to HWE, UAE resulted in higher yields, total sugar, uronic acid, and sulfate contents of AALPs. AALP prepared through UAE (AALP-U) exhibited better stability and stronger antioxidant activity compared to AALP prepared through HWE (AALP-H). In vivo antifatigue tests on mice showed that AALP-U significantly prolonged swimming time, increased liver and muscle glycogen levels, and improved biochemical indices, demonstrating its potential for use in functional foods. The study provides a theoretical basis and technical support for the application of AALPs in food and medicine.This study investigates the extraction and antifatigue activities of polysaccharides from *Artemisia argyi* leaves (AALPs) using ultrasound-assisted extraction (UAE) and hot water extraction (HWE). The optimal UAE conditions were determined to be 300 W ultrasonication power, 51 °C temperature, a liquid-to-solid ratio of 20 mL/g, and 47 minutes of ultrasonication time, yielding a maximum extraction rate of 10.49%. Compared to HWE, UAE resulted in higher yields, total sugar, uronic acid, and sulfate contents of AALPs. AALP prepared through UAE (AALP-U) exhibited better stability and stronger antioxidant activity compared to AALP prepared through HWE (AALP-H). In vivo antifatigue tests on mice showed that AALP-U significantly prolonged swimming time, increased liver and muscle glycogen levels, and improved biochemical indices, demonstrating its potential for use in functional foods. The study provides a theoretical basis and technical support for the application of AALPs in food and medicine.