The liver is responsible for the metabolism of the majority of currently utilized medicines and other foreign substances. Thioacetamide (TAA) is a potent hepatotoxin organosulfur compound. Moreover, TAA gained attention in research as a tool to induce liver injuries like inflammation, fibrosis, and cirrhosis, and to study liver regeneration. Several regimens are used to prevent and treat liver disease, but they have been linked with a variety of negative effects. Several natural substances have the potential to assist in the treatment and prevention of liver disease. Multiple mechanisms contribute to the efficacy of these herbal mixtures and their bioactive compounds in preventing and treating liver disease. TAA elicited the generation of ROS, provoked oxidative stress, and initiated apoptosis in hepatic cells via the JNK and MAPK pathways. Nevertheless, the adverse effects of TAA could be suppressed by natural plants, which not only eliminated ROS but also activated the PI3K-Akt cell survival pathway in the liver and prevented apoptosis approaches. Fuller understanding of the disease etiology and fibrotic processes is important for better prevention and treatment. This review aims to describe natural plant use in preventing and treating TAA-induced liver toxicity.