Huntington's disease (HD) is an inheritable autosomal dominant neurodegenerative disorder characterized by a clinical triad of progressive choreiform movements (dance-like movements), psychiatric symptoms, and a decline in the cognitive functions. It is caused by a CAG trinucleotide repeat expansion in the HD gene whereas principal pathology of this disease is the loss of striatal and cortical projection neurons. Different experimental animal models have been figured out to assist in understanding the mechanisms involved in the progress of the HD. Extensive researches had been done for testing a large array of neuroprotective agents using animal models which mimic such disorder and to examine the different mechanisms suggested to contribute in the progress of HD. Excitotoxicity in the central nervous system (CNS) results from glutamate exposure for prolonged periods or to excessive concentrations to glutamate. N-methyl-D-aspartic acid (NMDA) receptor is an ionotropic glutamate receptor responsible for the memory functions and exhibits several features of relevance to neuronal death. Neurotoxicity mediated by NMDA receptor with subsequent loss of striatal neurons contributes in the pathophysiology of HD. The current review focusing on using of NMDA receptor legends as a new strategy in treatment of HD.