Hepatotoxicity refers to structural or functional injury to the liver arising from exposure to natural toxins, metabolic by-products, or infectious agents. From a biomedical standpoint, hepatotoxicity is driven by mechanisms such as oxidative stress, mitochondrial dysfunction, immune-mediated injury, and disruption of bile transport pathways and further identifies patterns of injury—hepatocellular, cholestatic, or mixed—based on enzyme profiles. Drugs, alcohol, industrial chemicals, and natural toxins are key contributors to toxic liver injury in clinical practice. Ayurveda describes a remarkably parallel conceptual framework. Hepatotoxicity aligns broadly with Yakrit-Vikara arising from Pitta, Rakta, and Ama vitiation, where toxic or improperly metabolized substances impair the liver’s transformative and detoxifying capacities. The ingestion of Ahita (unwholesome foods), Dushi-varga dravyas (chronic low-grade toxins), contaminated food, and virulent biological agents correspond closely to the modern idea of hepatocellular insults. Classical texts further describe Yakrit Dushti arising from metabolic burden, mirroring modern concepts of lipotoxicity and Fatty Liver disease. Thus, both systems recognize the Liver as a central organ of metabolism and toxin clearance, and both attribute hepatic injury to overload, impaired transformation, and toxic accumulation—offering converging explanatory models and complementary strategies for prevention, early recognition, and management.