Anthocyanins are valuable natural pigments, but their practical application is limited due to their degradable nature in complex food matrices. To improve processing stability, this study combined docking-guided protein screening with experimental verification. Four conventional proteins were selected based on low binding energies. Complexation with the selected proteins, especially BSA and Zein, promoted the thermal persistence of ACNs, resulting in markedly higher retention rates. Multi-spectroscopic analysis revealed notable differences in binding mechanisms and conformational responses among the proteins. Within pH 4.0–6.0, BSA and Zein provided stronger stabilization of ACNs than PPI and WP, and binding induced local rearrangements of protein secondary structure, with Zein-ACNs complexes showing more pronounced spectral changes. These findings help relate protein structural features to ACNs stabilization and support the selection of protein carriers in mildly acidic food systems.