This study was carried out to investigate the acute toxicity and safety of Ssanghwa-tang extract fermented with Ganoderma lucidum. To evaluate the acute toxity and safety, 0(control group), 1250, 2500 and 5000 mg/kg of Ssanghwa-tang and fermented Ssanghwa-tang extracts were orally administered to 20 male and 20 female ICR mice. After single administration, we observed survival rates, general toxicity, changes of body weight, and autopsy. Compared with the control group, we could not find any toxic alteration in all treated groups (1250, 2500 and 5000 mg/kg). $LD_{50}$ of Ssanghwa-tang and fermented Ssanghwa-tang extracts might be over 5000 mg/kg and it is very safe to ICR mice.