Objective(s): The drinking of ethanol causes the wide range of clinical illness and morphological changes including hepatotoxicity and nephrotoxicity. In the current study, the protective properties of crocin versus oxidative stress, apoptosis and inflammation induced by ethanol were assessed. Materials and Methods: The male Wistar rats were divided into seven groups consisting of 6 rats in control, ethanol (50% v/v - 5 g/kg), crocin (10, 20 and 40 mg/Kg) plus ethanol, crocin 20 and 40 mg/Kg.Results: The MDA level was remarkably enhanced, while the content of GSH was significantly diminished in the kidney and liver of alcoholic rat but protective groups restored the level of MDA and GSH contents. Ethanol consumption induced hepatotoxicity and nephrotoxicity as evidenced by biochemical abnormalities and histopathological damages but crocin improved them. Also, crocin restored the TNF-α and IL-6 levels in the liver. The consumption of ethanol enhanced the levels of caspase-3, -8, -9 and Bax/Bcl-2 ratio (mRNA and protein) but, western blot and real-time PCR data confirmed that crocin treatment prevented apoptosis induced by ethanol.Conclusion: This research demonstrates that crocin has protective activities against ethanol toxic effects in rat liver and kidney via anti-inflammatory, antioxidant, and anti-apoptotic effects.