Neurotoxicity is caused by damage to the brain tissue by neurotoxic agents present in the environment and artificial substances produced by human beings. Acrylamide (ACR) is one such chemical substance that causes neurotoxicity, affecting the brain cells. This neurotoxicity causes damage to the sensory and metabolic functions. The current research investigates the favourable effect of probiotic EcN (Escherichia coli Nissle 1917) on ACR-induced neurotoxicity in zebrafish. The protective role of EcN against ACR induced toxicity was assessed based on behaviour, biochemical, and gene expression analysis. Initially, the colonisation period of EcN in the zebrafish gut was determined and EcN was given orally to the zebrafish only once prior to the ACR treatment. Very interestingly, this dosage was able to ameliorate the adverse effects of ACR significantly in the brain cells. Quantification of oxidative stress and neuronal cell death clearly vindicate the efficiency of probiotic EcN in reversing the damages caused by ACR. EcN is being explored largely in recent days for its therapeutic applications. This study strongly supports the view that EcN can be developed as a supplement to the patients diagnosed with neuronal cell toxicity.