Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are in order, a viral infection, a metabolic disorder, an ischemic event, and a neurodegenerative disorder. OS may be an early initiator or a significant promotor of their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology may avoid subsequent severe and irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, and autoimmunity. Past clinical studies that addressed OS have had equivocal results. It may be due to the use of ineffective antioxidants, an untimely delay in their use, or an inefficient delivery system. Experimental studies have used antioxidants that are not available for clinical trials. Although GSH can significantly reduce OS, its exogenous use is hampered by the lack of an effective delivery system. By incorporating GSH into cyclodextrin (CD) through nanotechnology, there is recent evidence that exogenous GSH can be delivered more effectively to prevent or mitigate injury from OS [1]. Future studies using the GSH/cyclodextrin (GC) complex will be needed to confirm its effectiveness and, hopefully, offer a path to treat many sub-optimally managed or currently untreatable illnesses.