As nonselective cation channels, transient receptor potential melastain 2 (TRPM2) channels are widely distributed in the brain, mainly mediate the inflow of Na+ and Ca2+, leading to cell depolarization and the increasement of intracellular concentration of Ca2+, which are involved in many physiological and pathophysiological processes. Due to increased calcium concentration or oxidative stress, channel gating is inducedeither direct or indirect formation of adenosine diphosphate ribose (ADPR) that binds to a NUDT9 homology domain (NUDT9-H) in the channel. There is no specific TRPM2 antagonist so far. Considering some pathological processes are mediatedTRPM2 channels, the study and discovery of specific TRPM2 blockers might contribute to the effective treatment of many related diseases.