The present study aims to use a natural protein silk fibroin (SF) to enhance solubility, dissolution, tablettability, and subsequently, delivery of naproxen (NP) using a green technique - ball milling. The development of SF and NP solid dispersion (SF-NP-SD) for enhancing the solubility, dissolution, and compatibility of NP using ball milling. In silico molecular docking indicated a strong binding affinity of SF towards NP. Herein, SF-NP-SD (1:1) showed significant improvement (p < 0.05) in saturation solubility (12 fold) and dissolution (1.46 fold) of NP. Along with reduced wetting time (p < 0.05), optimum values of flowability, compressibility, and compatibility were noteworthy. The spectroscopic analysis confirmed favorable interactions, amorphization, and stabilization of NP. The tablet formulation of SF-NP-SD exhibited 1.38-fold enhanced dissolution. Molecular-level hydrophobic and hydrophilic interactions of SF favor molecular-level dispersion, enhance solubility and dissolution, and consecutively, improve drug delivery of NP.