DehydroevodiamineㆍHCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impair-ment and depression induced by stress.