There are many causes of acute liver injury (ALI), such as alcohol, drugs, infection, and toxic materials, which have caused major health problems around the world. Among these causes, alcohol consumption induced liver injury is a common alcoholic liver disease, which can further lead to liver failure even liver cancer. A number of traditional Chinese medicine (TCM) and TCM derived compounds have been used in treating the liver-associated diseases and combination use of probiotics with TCM phytochemicals has attracted interests for enhanced biological effects. This study investigated the hepatoprotective effect of TCM-probiotics complex (TCMPC) and its underlying mechanism for the treatment of ALI in mice. The TCMPC is composed of TCM phytochemicals puerarin, curcumin, ginsenosides, and 5 lactobacteria strains. We first established a mouse model of alcohol-induced ALI, then the therapeutic effects of TCMPC on alcohol-induced ALI were monitored. A series of measurements have been performed on antioxidation, anti-inflammation, and lipid metabolism regulation. The results showed that TCMPC can reduce the level of liver injury biomarkers and regulate oxidative stress. Histopathological results indicated that TCMPC could ameliorate ALI in mice. In addition, it can also significantly reduce the production of inflammatory cytokines caused by ALI. Our research has proved the therapeutic effect of TCMPC on alcohol-induced ALI. The potential mechanism of hepatoprotective effects of TCMPC may be related to its antioxidative and anti-inflammatory effects. Our research might provide a new way for liver disease treatment.