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Polygonum multiflorum (PM), a commonly used Chinese herbal medicine in clinical practice, has been associated with frequent reports of liver injury in recent years, and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury (DILI) and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways, and it leads to the death of hepatocytes by destroying mitochondrial function, exacerbating bile acid accumulation, and inducing immune response, oxidative stress, and endoplasmic reticulum stress, thereby inducing the development and progression of DILI through multiple targets, pathways, and levels.
