In this study, the acute toxicity of Dendropanax morbiferus H.Lév leaf hot-water extracts (DMWE) was examined in male and female ICR mice. Mice were orally administered the DMWE at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no significant differences in change of BW between control and all DMWE treated-groups. In hematological and blood biochemical analysis, none of the parameters were affected by the DMWE. Similarly, there were no significant effects on markers for liver and kidney functions in all DMWE treated-groups. Since there were no adverse effects of the DMWE in single oral toxicity tests, even at the highest doses, it was concluded that the lethal dose 50 (LD50) of DMWE is estimated at > 2,000 mg/kg BW.