Gambihwan is a herbal prescription used in Korean medicine to treat obesity. The authors evaluated the effects and mechanisms of two types of Gambihwan (GBH1 and 2) administered to high-fat diet- (HFD-) induced obese mice. Four-week-old C57BL/6 mice were fed a HFD for 8 weeks with or without GBH1 or 2 (100-200 mg/kg/day by oral gavage). All mice were subjected to glucose tolerance testing after the 8-week treatment period and then euthanized. Serum insulin, lipids, and inflammatory cytokine levels were analyzed using commercial kits. Hepatic enzyme levels and lipid profiles were also investigated. Liver section slides were stained with Oil Red O (ORO) or hematoxylin and eosin (H&E) to assess lipid accumulation. GBH1 and 2 both significantly decreased body, liver, or adipose tissue weights in HFD-fed mice and significantly improved glucose tolerance (p<0.05 in all groups). Cholesterol levels in both sera and liver homogenates were significantly decreased by GBH1 and 2 (p<0.05 in all groups). In addition, serum inflammatory cytokines (p<0.05 in 200 mg/kg/day groups) and hepatic enzyme levels were significantly diminished by GBH administration at 200mg/kg/day (p<0.05 in all groups). Furthermore, histologic analyses of liver sections revealed GBH suppressed lipid accumulation. Both GBH types suppressed HFD-induced increases in body weight and obesity-related markers in HFD-fed mice despite the difference in constituents between GBH1 and 2. It is strongly assumed that the combination of Ephedrae herba and Coicis semen exerted the antiobesity effect. The results obtained show that the antiobesity effects of GBH warrant further investigation.