The protective effects of soyasaponins-rich extract (SRE) from soybean against acute alcohol-induced hepatotoxicity were first investigated in the Institute of Cancer Research mice. Administration of SRE prior to alcohol significantly prevented the increases in serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase caused by alcohol, as well as hepatic triglyceride, total cholesterol, and malondialdehyde levels. Mice treated with SRE showed a better profile of the antioxidant system with normal superoxide dismutase, glutathione S-transferase, and glutathione peroxidase activities, which were associated with the increase of hepatic glutathione levels relative to the acute alcohol-treated group. Supplement of SRE prevented alcohol-induced hepatic steatosis necrosis, inflammation, and swelling, as indicated by liver histopathological studies. All of these findings demonstrate that SRE has protective effects on acute alcohol-induced liver damage.