ABSTRACT Fungal keratitis (FK) is an extremely blinding infectious ocular surface disease. Clinically, there are three major challenges in the topic drug treatment of FK: poor corneal permeability, poor antifungal effect, and inability to simultaneously reduce the inflammation accompanying the infection. In this work, atomically dispersed Cu‐N 4 and Cu nanoclusters is designed loaded on the a small‐sized positively charged CDs (denoted as Cu‐SA/NC@CDs) is designed to fabricate Cu‐Needs. The Cu‐Needs exhibited excellent corneal permeability, which could can temporarily open the tight connections between corneal cells. More importantly, Cu‐Needs achieve rapid fungal elimination and eradication through energy depletion in fungus in the early stage of FK. Subsequently, Cu‐Needs effectively eliminated ROS and alleviated the inflammation in cornea tissue. This work proposes a strategy for the whole‐process intervention of fungal keratitis by regulating the microenvironment of single‐atom centers and nanoclusters through a tandem effect and enhancing catalytic activity. Conclusively, the excellent biosafety (biocompatibility, irritancy, ocular local toxicity and systemic toxicity) made Cu‐Needs a great potential strategy in clinical treatment of FK and other serious infectious diseases.