Oxidative stress plays an essential role in neurodegenerative pathophysiology, acting as both a critical signaling mediator and a driver of neuronal damage. Hydrogen sulfide (H2S), a versatile gasotransmitter, exhibits a similarly “Janus-faced” nature, acting as a potent antioxidant and cytoprotective molecule at physiological concentrations, but becoming detrimental when dysregulated. This review explores the dual roles of oxidative stress and H2S in normal cellular physiology and pathophysiology, focusing on neurodegenerative disease progression. We highlight potential therapeutic opportunities for targeting redox and sulfur-based signaling systems in neurodegenerative diseases by elucidating the intricate balance between these opposing forces.
