Drug-induced liver injury (DILI) is one of the common clinical adverse drug reactions and remains a major cause of drug restriction, development termination and withdrawal from the pharmaceutical market today. In recent years, a variety of chemical components and metabolites of traditional Chinese medicine (TCM), as well as the endogenous effector substances influenced by metabolism of both, have attracted much attention for their significant hepatoprotective activities. However, the mechanism of TCM against DILI is complex, the related effector substances are still unclear, and its metabolism-related studies are still relatively weak. Therefore, this review summarized the mechanisms of DILI and its treatment by TCM from the perspective of metabolism, and for the first time, innovatively classified the Chinese medicine effector substances into two categories: exogenous (active components and metabolites of TCM) and endogenous (intestinal probiotics and endogenous metabolites), in order to reduce the occurrence of DILI, explore and develop effective anti-drug-induced liver injury effector substances of TCM, and further develop clinical drugs with hepatoprotective effects.