$Lysimachia$ $foenum-graecum$ has been used as an oriental medicine with anti-inflammatory effect. The anti-obesity effect of $L.$ $foenum-graecum$ extract (LFE) was first discovered in our screening of natural product extract library against adipogenesis. To characterize its anti-obesity effects and to evaluate its potential as an anti-obesity drug, we performed various obesity- related experiments $in$ $vitro$ and $in$ $vivo$. In adipogenesis assay, LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of $2.5{mu}g/ml$. In addition, LFE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes $in$ $vitro$ at $10{mu}g/ml$ and $in$ $vivo$ at 100 mg/kg/day. The anti-adipogenic and anti- lipogenic effect of LFE seems to be mediated by the inhibition of PPAR${gamma}$ and C/EBP${alpha}$ expression as shown in $in$ $vitro$ and $in$ $vivo$, and the suppression of PPAR${gamma}$ activity $in$ $vitro$. Moreover, LFE stimulated fatty acid oxidation in an AMPK-dependent manner. In high-fat diet (HFD)-induced obese mice (n = 8/group), oral administration of LFE at 30, 100, and 300 mg/kg/day decreased total body weight gain significantly in all doses tested. No difference in food intake was observed between vehicle- and LFE-treated HFD mice. The weight of white adipose tissues including abdominal subcutaneous, epididymal, and perirenal adipose tissue was reduced markedly in LFE-treated HFD mice in a dose-dependent manner. Treatment of LFE also greatly improved serum levels of obesity-related biomarkers such as glucose, triglycerides, and adipocytokines leptin, adiponectin, and resistin. All together, these results showed anti-obesity effects of LFE on adipogenesis and lipid metabolism $in$ $vitro$ and $in$ $vivo$ and raised a possibility of developing LFE as anti-obesity therapeutics.