Corneal neovascularization (CNV) is a vision-threatening condition characterized by the pathological ingrowth of blood vessels. While corticosteroids and anti-VEGF agents are standard treatments, their prolonged use is associated with significant ocular side effects. This study aimed to develop and optimize nanosuspensions of Apigenin (APG) and Apigenin-7-O-glucoside (APG-7) to enhance their ocular bioavailability and evaluate their efficacy in the treatment of CNV. APG and APG-7 were isolated from Petroselinum crispum. Nanosuspensions were formulated using an anti-solvent precipitation method, optimized via a 23 factorial design considering PVA concentration, Span 80 concentration, and homogenization speed. The physicochemical properties, including particle size, PDI, and zeta potential, were characterized. In vivo efficacy was assessed in an alkali-burn induced rat CNV model through clinical scoring, histopathology, and immunohistochemical analysis of VEGFA and IL-6 expression. The optimized APG nanosuspensions exhibited a mean particle size of ~166.9 nm with high stability. In vivo studies demonstrated that 0.05% APG nanosuspension significantly inhibited corneal angiogenesis, reduced stromal edema, and downregulated VEGFA and IL-6 expression compared to the untreated injury group (p < 0.05). Conversely, APG-7 formulations failed to show significant therapeutic efficacy, likely due to limited corneal permeability attributed to the glycoside moiety. The 0.05% APG nanosuspension presents a promising, non-invasive therapeutic alternative for CNV management, offering effective anti-angiogenic activity with improved ocular delivery characteristics.