BACKGROUND: Chronic alcoholism refers to the unpleasant symptoms directly resulting from excessive drinking. Increased alcohol metabolites and an unbalanced oxidative state are likely to blame for the reported effects under these circumstances. According to preclinical and clinical research, vitamin B12 can act on several organ systems with demonstrated neuroprotective, antioxidant, and glutamate modulating properties. OBJECTIVE: This research sought to examine the ameliorative effects of vitamin B12 (VtB12) in persistent alcohol (AlOH) exposed adult zebrafish with the help of following parameters like the anxiety related behavior test, Oxidative stress, and antioxidant assays, histological and immunofluorescence analysis. METHODS: Zebrafish pretreated with 0.40% AlOH (v/v) for 120 min (+AlOH) or not (-AlOH), were exposed for 6 h to home tank water (-VtB12) or to 59 µg-VtB12/kg-fish food (+VtB12) to analyze anxiety behavior in the geotaxis (novel tank) test as well as the oxidative brain damage in the adult zebrafish. RESULTS: Adult zebrafish exposed to chronic AlOH showed a decrease in the distance travelled, average and mobility speed, and increased the average frozen time, the explored area, and total no. of the site explored in the trapezoid tank. AlOH exposure also resulted in oxidative damage, enhanced lipid peroxidation, advanced oxidative protein products, decreased enzymatic and non-enzymatic antioxidant activities, and enhanced reactive oxygen species generation. Additionally, VtB12 supplementation improved neurogenesis, evident in increased Nissl cell numbers and NeuN expression in the brain. CONCLUSION: Chronic alcoholism may be effect on the brain cells as well as on the neuro-behavior of zebrafish. This research demonstrated that VtB12 shows promise as a neuroprotective agent against chronic alcoholism induced alterations in zebrafish's brain.