Obesity is a metabolic disorder characterized by chronic inflammation and dyslipidemia and is a strong predictor for the development of hypertension, diabetes mellitus, and cardiovascular disease. This study examined the antiobesity effect of an ethanol extract of Corni Fructus containing formulation (CDAP), which is a combination of four natural components: Corni Fructus, Dioscoreae Rhizoma, Aurantii Fructus Immaturus, and Platycodonis Radix. The cellular lipid content in 3T3-L1 adipocytes was assessed by Oil Red O staining. Expressions of peroxisome proliferator-activated receptor- γ (PPAR- γ ), CCAAT/enhancer-binding protein- α (C/EBP- α ), and lipin-1 were determined by real-time RT-PCR. Western blot was used to determine the protein levels of PPAR- γ , C/EBP- α , and AMP-activated protein kinase- α (AMPK- α ). The CDAP extract suppressed the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of PPAR- γ , C/EBP- α , and lipin-1. The CDAP extract also significantly upregulated phosphorylation of AMPK- α . An in vivo study showed that CDAP induced weight loss in mice with high-fat-diet-induced obesity. These results indicate that CDAP has a potent anti-obesity effect due to the inhibition of adipocyte differentiation and adipogenesis.