Chemical modification of silk materials is a powerful method of tailoring the desired physical properties for possible application in various fields. In this work, we modified silk fibroin with poly(2,6-dimethyl-1,5-phenylene ether) (PPE) in order to imbue the silks with hydrophobicity so as to resist the absorption of humidity. This modification was achieved through the chemoenzymatic polymerization of 2,6-dimethylphenol (DMP) using horseradish peroxidase (HRP) as a catalyst in the presence of silk fibroin obtained from Bombyx mori. The PPE chain content in the modified silks was tuned by varying the feed concentration of DMP. Wide-angle X-ray scattering measurements revealed that β-sheet crystalline structures were formed in the PPE-modified silks, even after the introduction of bulky PPE chains. The PPE-modified silks showed glass transitions derived from the PPE domains, which enabled the formation of self-standing films upon thermal processing. Films of the PPE-modified silks exhibited higher static contact angles of water droplets compared to the native silk films, indicating that the film surface of silk fibroin became more hydrophobic because of the introduction of PPE. These improved physical properties were achieved without sacrificing the inherent secondary structure of silk fibroin, namely, the β-sheet structure that dominates the mechanical properties of silk materials.