Jian Gan powder (JGP), a traditional Chinese medicine (TCM) formula, has been found to have considerable protective and therapeutic effects on hepatitis virus-induced immunological liver injury (ILI) in the clinic. However, the mechanism through which JGP achieves an optimal hepatoprotective effect remains unclear.In this study, JGP treatment markedly reduced ILI mice serum interferon-gamma (IFN-r), interleukin 6 (IL-6), IL-22, and hepatic p-STAT3 expression. In contrast, JGP treatment elevated the ratio of proliferating cell nuclear antigen (PCNA)-positive liver cells in the ILI mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the dysbiosis of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics analysis showed that the metabolites, allylestrenol, eplerenone, PE (P-20:0/0:0), SM d27:1, soyasapogenol C, chrysin, and soyasaponin I were notably changed and remarkably reversed after JGP treatment. The results of this study show that JGP exerts anti-inflammatory and pro-proliferative effects and restores the dysbiosis of the gut microbiota and metabolism of the ILI mice. These results provide a new perspective and indicate that intestinal microbiota and their metabolites might be potential targets for elucidating the mechanism of JGP on improving ILI.