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This review focuses on I3C potential role in preventing and repairing damage caused by chemicals and drugs. Interestingly, I3C ameliorates hepatotoxicity induced by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>), diethylnitrosamine (DENA), alcohol, gold nanoparticles, and microbial toxins. Additionally, it inhibits carcinogenesis induced by different chemicals and prevents the deleterious effects of different antineoplastic drugs including cisplatin, doxorubicin (DOX), and trabectidin on normal tissues. Moreover, it reduces fetal malformation and protects against micronuclei formation and calstogenecity induced by cyclophosphamide (CP) in bone marrow cells. It also attenuates methotrexate (MTX)\u2010induced hepatotoxicity, mitigates neurotoxicity caused by thioacetamide and clonidine, and protects against aspirin side effects in gastric mucosa. Furthermore, its nanoparticles inhibit neuronal damage caused by glutamate and rotenone. 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