This study was performed to elucidate the effect and underlying mechanism of Jinmutang-hap-Banggihwanggi-tang Gagam extract (JB) in high-fat diet (HFD)-supplied obese mice. Male C57BL/6 mice were administrated with distilled water, Garcinia gummi-gutta exteact (GGE), or JB for 6 wks with HFD feeding. Mice were divided into five groups (n=7): Group I - general diet and untreated group, Group II - HFD control group, Group III (GG) - HFD+GGE (200 mg/kg), Group IV (JBL) - HFD+JB (1.49 g/kg), Group V (JBH) - HFD+JB (2.98 g/kg). Hematoxylin and eosin and Oil red O staining were performed for histological examination. Western blot analysis was used to detect the protein expression of Sirtuin 1 (SIRT1), phosphorylated AMP-activated protein kinase α (AMPKα), and the proteins involved in lipogenesis and β-oxidation. Moreover, the amount of glycerol released in fat tissues was measured for lipolysis activity. JB dramatically reduced body weight gain, liver, and epididymal fat weights. In addition, serum lipid profiles by JB administration ameliorated compared with those of mice only HFD fed. Furthermore, the protein expressions of p-AMPK and SIRT1 were markedly increased in JB-treated mice. JB not only upregulated the expression of proteins such as PPARα, PGC-1α, UCP2, CPT-1A involved in β-oxidation, but also downregulated levels of transcription proteins such as SREBP-1 and SREBP-2 and its downstream factors related to lipogenesis. JB improved HFD-induced lipid accumulation in liver tissues. Especially, the ameliorative effect of JBH was superior to those when JBL. We demonstrated that JB treatment significantly ameliorated obesity by regulating both lipogenesis and β-oxidation via the activation of the AMPK/SIRT1 pathway. The current study could provide basic information for the anti-obesity effect of Jinmutang-hap-Banggihwanggi-tang Gagam on diet-induced obesity.