Abstract: Glutathione (GSH) plays a critical role in cellular redox homeostasis and disease diagnosis, necessitating its efficient detection for biomedical applications. Oxidase (OXD)-like nanozymes offer advantages by eliminating the need for additional oxidants, yet their prolonged exposure to oxygen (O₂) often leads to activity decay, limiting practical applications. Here, we report the construction of a light-responsive polyphenol-based carbon dot nanozyme (E-CDs) leveraging the interfacial modulation capabilities of plant polyphenols. E-CDs exhibit exceptional fluorescence stability and OXD-like activity. Under UV-LED irradiation, E-CDs catalyze O₂ to generate reactive oxygen species (ROS), while surface polyphenol moieties selectively recognize and capture GSH, facilitating ROS scavenging and enhancing detection sensitivity. This strategy overcomes the intrinsic activity decay of conventional OXD-like nanozymes, achieving an ultra-low detection limit of 5 nmol L^–1. Our work provides a novel approach for ultrasensitive GSH detection and expands the potential applications of light-responsive nanozymes in biosensing.