Abstract Background: Cooking carbohydrate-rich dietproduce acrylamide chemical (ACR) that exerts a hepatotoxic and neurotoxic effects. Daphnetin (DAPH), a coumarin derivative, has been reported for its potential therapeutic effects. Aim of Study: Toevaluate the effect of DAPH on hepato-and neurotoxicity of ACR. Material and Methods: We investigated the effect of DAPH on the hepatic and neural impairment caused by expo-sure to ACR (40mg/kg) for 15 days in mice. Liver function tests and oxidative stress markers were estimated. Further, the expression level of tumor necrosis factor alpha (TNF-a), hemeoxygenase-1 (HO-1) and caspase-3 activity were assessed in brain and liver tissues. Results: The administration of DAPH (20 mg/kg) to ACR-intoxicated mice significantly decreased the serum levels of transaminases; with improving the protein and albumin content impairment of liver caused by ACR. The level of malondial-dehyde (MDA) significantly decreased in the brain tissue of mice treated with DAPH after the drastically increase of MDA caused by ACR intoxication. DAPH administration down regulate Caspase 3 and TNF-a after their up-regulation in the ACR group while DAPH administration up-regulate HO-1 after the significant down-regulation by ACR. Conclusion: In conclusion, our results highlight that exposure to DAPH assuaged ACR-induced oxidative stress, inflammation and caspase-3 activation in liver and brain of mice. Thus, DAPH could be effective in reducing hepato- and neuro-toxicity due to its strong antioxidant, anti-inflammatory and antiapoptotic properties.