Alcoholism is a serious problem throughout the world. Despite intensive efforts to develop novel therapeutics for strategy efficacy against neuronal loss leading to memory impairment in alcoholism is still limited. In view of the pitfalls of psychological dependence and adverse behavioral effects of synthetic drugs, the development of low toxicity and high efficiency medicines derived from natural herbal antioxidants exhibits expansive market prospects. In this respect, Coscinium Fenestratum (C. Fenestratum; CF) could be an attractive candidate as a diet supplement for neuroprotactant against ethanol-induced neurodegeneration. Herein, we determined the neuroprotective effects of CF against ethanol-induced neuronal damage in both hippocampus and cerebral cortex. The stems of CF extract (No. HHP-2-462) were dried, refluxed with ethanoland evaporated with lyophilizer. Extract was gave a yield of 8.53%. The rats were pretreated with the extract at various doses ranging from 5, 10 and 20 mg kg −1 once daily per os, 30 min prior to ethanol administration at a dose of 1.8 g kg −1 via i.p for 14 consecutive days and were evaluated the densities of survival and cholinergic neurons in all areas as mention above by immune histological techniques. CF extract at a dose of 5 mg kg −1 showed the attenuation of the neurotoxicity in all brain areas just mentioned except in the temporal cortex. In addition, it also mitigated the degeneration of cholinergic neurons in all areas of hippocampus except in CA3 region. This study indicated that CF extract consumption may be served as a diet supplement protect against neuronal degeneration resulting from excessive continuous consumption of alcohol. However, further researches about possible active ingredients and pharmacokinetic of the extract are still required before moving forward to clinical trial study.