Biomolecule grafting on polyether ether ketone (PEEK) was used to improve cell affinity caused by surface inertness. This study demonstrated the sequence-polished (P) and sulfonated (SA) PEEK modification to make a 3D structure, active biomolecule graftings through PEEK silylation (SA/SI) and then processed with phosphatidylcholine (with silylation of SA/SI/PC; without SA/PC) and type I collagen (COL I, with silylation of SA/SI/C; without SA/C). Different modified PEEKs were implanted for 4, 8, and 12 weeks for histology. Sulfonated PEEK of SA showed the surface roughness was significantly increased; after the silylation of SA/SI, the hydrophilic nature was remarkably improved. The biomolecules were effectively grafted through silylation, and the cells showed improved attachment after 1 h. Furthermore, the SA/SI/PC group showed good in vitro mineralization. The new bone tissues were integrated into the 3D porous structures of SA/SI/PC and SA/SI/C in vivo making PEEK a potential alternative to metals in orthopedic implants.