Nowadays, the drug induced organ damage has increased drastically. Similarly, number of Adverse Drug Reactions (ADR) is on the rise. Unwanted and harmful effects of a drug have been a good reason for early withdrawal of a good molecule from the market or clinical trial. In the present study, we have investigated the preventive role of Syzygium cumini against Acetaminophen induced organ damage. In this study, four different groups of rats were evaluated. Group A serves as a control group, Group B serves as control + Syzygium cumini group, Group C serves as disease group and Group D serves as disease + treatment group. Only two groups have been treated and exposed to an overdose of acetaminophen. However, liver and kidney markers like Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Alanine Transaminase (ALT), Creatinin and Uric acid (UA) were measured respectively. Moreover, oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO) and Advanced Oxidation Protein Product (AOPP) were found higher in acetaminophen overdose rats compared to control rats. Furthermore, antioxidant enzymes like Catalase (CAT), Superoxide Dismutase (SOD) and Linear Peptide Glutathione (GSH) were restored significantly by Syzygium cumini seed treatment. Finally, our study revealed that supplementation of 1% Syzygium cumini seed with food attenuated inflammatory cell infiltration, collagen secretion, extracellular matrix deposition and iron overload in both hepatic and kidney. We assume that the protection might be achieved due to having strong antioxidant properties of Syzygium cumini.