The critical role of nitric oxide (NO), a potent signalling molecule, in various physiological processes has driven the development of NO delivery strategies for numerous therapeutic applications. However, NO's short half-life poses a significant challenge for its effective delivery. Glutathione peroxidase, a selenium-containing antioxidant enzyme, can catalyse the decomposition of S-nitrosothiols (endogenous NO prodrugs) to produce NO in situ. Inspired by this, we explored selenium nanoparticles (SeNPs) for their enzyme-mimicking NO-generating activity. Stabilised with polyvinyl alcohol (PVA) or chitosan (CTS), SeNPs demonstrated tuneable NO generation when exposed to varying concentrations of NO prodrug, nanoparticles, and glutathione (GSH). In the presence of GSH, a naturally occurring antioxidant in the human body, 0.1 µg mL