One of the essential functions of the liver is drug metabolism and excretion or "biotransformation". The biotransformation process sometimes leads to the generation of free radicals causing oxidative damage. This could directly or indirectly influence organelles causing cell death, making drug-induced liver injury the leading cause of liver injury. Methotrexate is a good representative for drug-induced liver injury with high rates of discontinuation due to its adverse side effects. Natural products are enriched with various phytochemicals that could protect not only the liver but even the whole body from the adverse side effects of the synthetic chemical drugs.