Herbal therapeutics such as curcumin have potent anti-inflammatory and antioxidant potential but face challenges of low solubility, poor bioavailability, and instability. Proniosomes, surfactant-coated dry vesicular carriers, offer enhanced stability, scalability, and bioavailability, making them suitable for delivering insoluble herbal actives through topical applications. This study was designed to develop and optimize curcumin-loaded Proniosomes using Box-Behnken Design (BBD) to improve physicochemical features for psoriasis management. Proniosomes were prepared by antisolvent precipitation using Span 80, soya lecithin, and cholesterol. A three-factor, three-level BBD was applied to evaluate the effect of Span (X₁), lecithin (X₂), and cholesterol (X₃) on critical quality attributes: particle size (Y₁), zeta potential (Y₂), and PDI (Y₃). Seventeen runs were performed and statistically analyzed using ANOVA, Pearson’s correlation, and lack-of-fit testing. Entrapment efficiency and in vitro drug release were further measured. Formulations showed particle sizes of 143–366 nm, zeta potential of 14–32 mV, and PDI of 0.045–0.53. The optimized batch exhibited ~206 nm particle size, ~24 mV zeta potential, and 0.22 PDI. Entrapment efficiency reached ~84%, while drug release was sustained over 24 h, with ~96.64% cumulative release at 48 h compared to ~25.5% for pure curcumin. Enhanced release was attributed to the amphiphilic surfactants forming stable bilayered vesicles, and cholesterol providing structural integrity for controlled release. In conclusion, optimized curcumin Proniosomes established high stability, scalability, entrapment, and sustained release, providing a promising topical delivery platform for effective psoriasis management.