Preventing prosthesis loosening due to insufficient osseointegration is critical for patients with osteoporosis. Endowing implants with immunomodulatory function can effectively enhance osseointegration. In this work, we loaded icariin (ICA) onto 3D porous sulfonated PEEK (SPEEK) via polydopamine (PDA) modification. Modified ICA-PDA@SPEEK not only promoted the polarization of macrophages to the anti-inflammatory M2 type, but also enhanced the osteogenesis of bone mesenchymal stem cells (BMSCs) and inhibited RANKL-induced osteoclastogenesis by regulating cytokine from macrophages. In vivo experiments further showed that ICA-PDA@SPEEK regulated the host immune response and promoted osseointegration in ovariectomized (OVX) rats. The above results demonstrated that ICA-PDA@SPEEK could be an excellent orthopedic biomaterial with immunomodulatory properties.