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ABSTRACTPolygonatum cyrtonema Hua polysaccharides (PCP) have beneficial effects on lipid metabolism and oxidative stress. Here, PCP extraction was optimized using response surface methodology (RSM), and the antioxidant and lipid-lowering effects of its main component, PCP1, were evaluated in vitro. The maximum PCP yield was 11.05% at an extraction temperature was 72°C, liquid-to-solid ratio of 21, extraction time of 96 min, and two extraction rounds. PCP1 was purified by column chromatography and showed significant scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and 2, 2'-azino-bis 3-ethylbenzthiazo-line-6-sulfonic acid (ABTS) radicals at concentration of 0.2–1.0 mg/mL. At a concentration of 200 [Formula: see text]g/mL, PCP1 significantly improved lipid disorder and damage induced by palmitic acid in HepG2 cells. These results show that PCP has potent antioxidant and lipid-lowering effects in vitro; moreover, the PCP extraction rate is significantly increased using RSM. Therefore, PCP is an effective antioxidant and lipid-lowering product with potential medicinal applications.