Significance Redox sensitivity is a common property of temperature-sensitive transient receptor potential (TRP) ion channels. Here we show that oxidation sensitizes and activates rodent TRPV2 orthologs known to have a high temperature threshold (>50 °C), but also the heat-insensitive human TRPV2. This oxidation-induced channel gating is intact in cell-free membrane patches, cysteine-independent but reduced upon replacement of the methionine residues M528 and M607. Blocking of TRPV2 and the reducing agent DTT reduce phagocytosis in macrophages which also generate heat-induced membrane currents following oxidation. These data reveal a methionine-dependent redox sensitivity of TRPV2 which may resemble a decisive endogenous mechanism enabling channel activation.