This reaction is catalyzed by the enzyme glutathione reductase.

[2] Antioxidant enzymes, such as glutathione peroxidases and peroxiredoxins, generate glutathione disulfide during the reduction of peroxides such as hydrogen peroxide (H2O2) and organic hydroperoxides (ROOH):[3] Other enzymes, such as glutaredoxins, generate glutathione disulfide through thiol-disulfide exchange with protein disulfide bonds or other low molecular mass compounds, such as coenzyme A disulfide or dehydroascorbic acid.

[4] The GSH:GSSG ratio is therefore an important bioindicator of cellular health, with a higher ratio signifying less oxidative stress in the organism.

[5] GSSG, along with glutathione and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators.

[6][7] At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex.