This study investigated the anti-obesity effect of Adenophora triphylla root ethanol extract (ATREE). C57BL/6 mice were divided into five groups, a normal diet group (N), a control group fed only high-fat diet (HFD) (C), a positive control group fed HFD with 0.5% catechin (PC), and groups fed HFD with 0.5% (E1) or 1% (E2) ATREE. The body weight gain, hematological and serum biochemistry data, and anti-oxidative index in the liver and epididymal adipose tissue were improved significantly in the E group (E1, E2), as compared to the C group. As for histological findings, adipocyte size was reduced by ATREE. E group (E1, E2) showed significant increases in adiponectin, AMPK, and PPAR-α, and significant decreases in TNF-α, GPDH, and PPAR-γ, as compared to the C group. The above findings indicate that ATREE might have an anti-obesity effect through antioxidant and anti-inflammatory action. It is considered ATREE can be used as a natural treatment for obesity and metabolic syndrome induced by oxidative stress.