A polyphenol-based eye drop is developed via the self-polymerization of rosmarinic acid in the presence hyaluronic acid, followed by co-assembly with cerium ions to afford monodispersed RHC NPs. To enhance the ocular retention efficiency, thiol groups are further decorated on NPs (termed as s-RHC NPs). In two mouse models of DED, topical administration of s-RHC NPs leads to comprehensive relief of symptoms, including inflammatory response suppression, corneal epithelial defect repair, and tear secretion recovery.