Natural products are widely used due to their various biological activities which include antiinflammatory, antioxidant, and anti-obesity effects. In this study, we determined the antioxidative and anti-obesity effects of Polygonum cuspidatum 50% ethanol extract (PEE). The antioxidative effect of PEE was evaluated using its radical scavenging activity, total phenoliccontent, and reducing power. The anti-obesity effect of PEE was investigated using 3T3-L1adipocytes. The antioxidative activity of PEE was progressively increased in variousconcentrations, mainly due to the presence of phenolic compounds. PEE also alleviated lipid accumulation on 3T3-L1 adipocytes and downregulated the mRNA and protein production of adipogenesis-related (SREBP-1c, PPAR
) and lipogenesis-related (aP2, FAS, ACC) markers. Furthermore, we found that the inhibitory effect on lipid accumulation via PEE was caused by the alleviation of NF-
B, p38 MAPK, ERK1/2, and JNK at the protein level. Taken together, our results imply that PEE is a potential antioxidant that can prevent obesityassociated disorders.