Abstract: Objectives: This study aimed to investigate the in vivo and in vitro antioxidant, anti-inflammatory, analgesic, and antimicrobial activities of crude polysaccharides from Polygonum erfoliatum L.. Methods: The crude polysaccharides were prepared using the water extraction and alcohol precipitation method. The in vitro antioxidant activity was assessed based on the capability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, hydroxyl radicals, and superoxide anion radicals. The in vivo antioxidant indicators were the determination of total superoxide dismutase (T-SOD) activity, catalase (CAT) activity, and malondialdehyde (MDA) content, providing a comprehensive evaluation of the antioxidant activity of the crude polysaccharides. The anti-inflammatory effect of the crude polysaccharides was assessed using the xylene-induced mice ear edema method. The analgesic effect was evaluated by determining the pain threshold in mice using the hot plate test. The in vitro antimicrobial activity was evaluated by the Oxford cup method. Results: The crude polysaccharides displayed effective scavenging abilities against DPPH radicals, hydroxyl radicals, and superoxide anion radicals, with the activity significantly dependent on the concentration of the polysaccharides. The half-maximal inhibitory concentration (IC₅₀) values were 420.93, 171.53, and 575.40 μg/mL, respectively. Compared to the control group, the polysaccharides enhanced the activity of T-SOD and CAT, reduced MDA levels in vivo. The crude polysaccharides inhibited xylene-induced swelling with an inhibition rate reaching 40.95%. However, the analgesic effect of the crude polysaccharides was not significant, and they showed no inhibitory effects against Escherichia coli and Staphylococcus aureus. Conclusions: The crude polysaccharides from Polygonum perfoliatum L. possess antioxidant and anti-inflammatory activities and have the potential to be developed as natural antioxidants.