The Transient Receptor Potential Melastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel and Adenosine 5'-DiphosPhatase Ribose (ADPR) hydrolase function. TRPM2 is involved in Ca2+ signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+ entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis. The wide expression of TRPM2 might render it as a potentially significant therapeutic target in pathological settings including cardiovascular and neurodegenerative diseases and of great relevance in drug design, feed additives and other industries. Here, we discuss the TRPM2 gene structure, function, its variants, as well as its activators and inhibitors and provide a peptide drug design for modulation of oxidative stress.