Cataract remains a major cause of ocular blindness. Cyclic Arg-Gly-Asp-d-Phe-Lys (RGD) peptide was introduced to the surface of self-assembled hybrid micelles for the co-delivery of poly (ADP-ribose) polymerase 1 (PARP-1) small-interfering RNA (siRNA) and quercetin (Q/siP-c-M). Q/siP-c-M exhibited uniform particle size distribution, good dispersibility, high encapsulation efficiency, and strong stability for siRNA and quercetin. Q/siP-c-M significantly improved the transcorneal co-delivery of siRNA and quercetin to the deeper cornea and led to greater drug accumulation. In addition, Q/siP-c-M significantly increased the activity of catalase and the content of adenosine triphosphate (ATP), reduced the expression of PARP-1 protein, and effectively prevented lipid peroxidation in the lens. Among selenite-induced cataract rats, the Q/siP-c-M-treated rats produced higher levels of ATP and catalase, as well as lower levels of malondialdehyde and PARP-1 protein expression compared with those in the model group. Administration of quercetin further resulted in a decrease in neutrophil extracellular trap formation and downregulation of gene expression of related proteins and pro-inflammatory cytokines. These observations indicated that quercetin has the potential to serve as a therapeutic for alleviating an excessive inflammatory reaction characterized by an overabundance of neutrophil extracellular traps in the eyes. Therefore, this study highlights the potential of Q/siP-c-M against cataract development through the regulation of the immune response by regulating inflammatory conditions. Furthermore, Q/siP-c-M may offer benefits in terms of apoptosis attenuation for lens epithelial cells.