A cocktail made with the extract of three medicinal plants (Spondias mombin, Vernonia amygdalina and Momordica charantia) is widely used in the traditional Ivorian pharmacopeia for the treatment of various illnesses and brain disorders. The present study aimed to evaluate the possible preventive effect of the hydroethanolic extract of the cocktail on anxiety and depression as well as memory disorders related to abrupt withdrawal from chronic alcoholism using a Mice model. Adult mice were either with vehicle (phosphate buffer saline, 1 ml/100 g, p.o.) or 20% of alcohol drink (2g/kg, p.o) for 28 days. Some alcoholic mice were concomitantly treated with cocktail extract (50 and 100 mg/kg, p.o). Twenty-four hours later, anxiety and depression-like behavior, and memory abilities were assessed with behavioral tests. The level of oxidative stress markers such as nitric oxide (NO), malondialdehyde (MDA) and non-protein-thiol (NP-SH) were assayed in hippocampus and prefrontal cortex. The results showed that the cocktail extract significantly prevented at dose-dependent manner the abrupt alcohol withdrawal-induced anxiety and depression-like behavior. In addition, the cocktail extract significantly improved the spatial learning and reference memory deficits observed in alcoholic mice. The results also revealed that the cocktail extract significantly mitigated the MDA and NO content, but in same time increased the level of NP-SH in both the hippocampus and prefrontal cortex when compared to chronic alcoholic mice. Our finding provides evidence that the cocktail of the three medicinal plants has neuroprotective effects against alcohol withdrawal symptoms and confirms its traditional use to relieve cognitive-affective disorders.