To elucidate the anorexigenic action and inhibitory effect of fat accumulation by epigallocatechin gallate (EGCG) and caffeine, including the optimal combination ratio and mechanism, fifteen diets with several concentrations of EGCG and/or caffeine were administered to mice for eight weeks. The 0.1% EGCG + 0.1% caffeine group showed the strongest suppression of food intake and a remarkable reduction of body weight and fat accumulation; therefore, the ratio was determined to be the optimal combination ratio. Moreover, serum glucagon-like peptide-1 (GLP-1) level and hypothalamic gene expression of pro-opiomelanocortin (POMC) were promoted by 0.1% EGCG + 0.1% caffeine. In conclusion, the combined treatment of 0.1% EGCG + 0.1% caffeine induces not only suppression of fat accumulation but also strong anorexigenic action in mice. The anorexigenic effect may be brought about via inhibiting gastric motility by GLP-1 and upregulating POMC in the hypothalamus.