Summary:This study prepared zein-rutin supramolecular nanoparticles using a pH-ultrasound-shifting method. The optimized Z-R-P-U system achieved 87.89 ± 1.28% encapsulation efficiency and 23.97 ± 0.56% loading capacity. Multispectral analysis and molecular docking indicated that hydrogen bonding, van der Waals forces, and hydrophobic interactions dominated zein-rutin binding. The nanoparticles were about 150 nm, remained below 200 nm after 28 days of storage, improved rutin solubility by 9.2-fold, and enhanced antioxidant activity, bioaccessibility, and controlled release behavior.