As the major neurotransmitter in the mammalian central nervous system (CNS), excessive extracellular glutamate (Glu) can activate the Glu receptors and neuronal calcium (Ca2+) overload, then produce neurotoxicity, which is a common pathway for neuronal injury or death, and is associated with acute and chronic neurodegenerative diseases. Therefore, it has been a therapeutic strategy to investigate neuroprotective effects against Glu-induced neurotoxicity for treating both acute and chronic forms of neurodegeneration. Resveratrol (Res), as a naturally occurring polyphenol mainly found in grapes and red wine, has shown a neuroprotective effect in a variety of experimental models for neurodegenerative diseases in vitro and in vivo. This review will focus on the neuroprotective effect of Res against Glu-induced excitotoxicity in neurodegenerative diseases by blocking different Glu receptors and Ca2+ ion channels.