Spermidine is a natural polyamine and has effects on modulation of synapse plasticity, anti-oxidative stress, and the activation of autophagy. This article reviewed the neuromodulative and neuroprotective effects of spermidine in nervous system to provide novel insights into the specific mechanisms of the neuromodulative and neuroprotective action underlying spermidine.Keywors: spermidine; synapse plasticity; oxidative stress; autophagy; neuromodulative and neuroprotective