Glutathione (GSH), a naturally-occurring tripeptide, plays an important role as an intracellular antioxidant in the physiological microenvironment and participates in redox balance, detoxification, cellular and disease regulation. The unique structural features of GSH, including the reductive thiol and multiple coordination sites (carboxyl and amino group), empower its remarkable contributions beyond physiological roles but as a ligand in the development of functional metal nanomaterials. In this context, GSH’s role as a protective ligand and reducing agent in surface etching and ligand exchange reactions has been explored at the molecular level, expanding the diversity of GSH-protected metal nanomaterials. With photoluminescence (PL) as one of its most intriguing properties, investigations into GSH’s influence on PL properties emphasize its multifaceted coordination capabilities in surface coating, charge transfer from electron-rich functional groups, chirality arising from its unique structure, and available conjugation sites. Moreover, the biocompatibility of GSH, combined with the synergistic effect of metal components, renders GSH-protected nanomaterials an “Inseparable Duo” highly suited for applications in bio-sensing, bio-imaging via PL radiative decay and anti-cancer bio-therapies through photothermal therapy, photodynamic therapy, and radiotherapy. By exploring the multifaceted roles of GSH, this Perspective aims to highlight pathways including the encouragement of deeper synthetic exploration, innovative design at the bio-nano interface, and expanded nanobiomedical applications.
