Chemicals (such as alcohol, drugs, and pollutants) may cause liver injuries, which could consequently develop into fatty liver, hepatitis, fibrosis, cirrhosis, and liver failure, or even cancers. Liver injuries have been a serious public health problem worldwide. Numerous natural products and their bioactive components have shown protective action for liver injuries, such as blueberry, cactus fruits, Pueraria lobate, betaine, and silymarin. The underlying mechanisms mainly include antioxidation, anti-inflammation, anti-apoptosis, anti-necrosis, repairing damaged DNA, regulating the metabolism of lipids, and modulating primary bile acid biosynthesis. This review summarizes the natural products and bioactive compounds with protective effects on liver injuries caused by chemicals, and special attention is paid to the mechanisms of action. This updated information can be helpful to prevent and treat liver-related diseases, especially chemical-induced liver injuries.