Neurodegenerative diseases refer to incurable conditions that result in progressive degeneration or death of nerve cells. This causes functional movement deficits and cognitive problems such as dementias. Among different types of neurodegenerative diseases, Alzheimer disease (AD) accounts for majority of the cases. The transient receptor potential melastatin member 2 (TRPM2) channel is a Ca2+-permeable non-selective cation channel which has been studied and implicated in the pathological process of AD through different pathways including inflammation. This review summarizes the contribution of TRPM2 in AD pathology and recent advances in pharmacology of TRPM2, with a focus on relationships between β-amyloid, oxidative stress and Ca2+. We also discuss the potential future research direction for neurodegenerative diseases.