Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements. A dual-effect of host defense and tissue repair can be rationally constructed by bioorthogonal conjugations of both anti-infective and osteo-inductive peptides on PEEK osteoimplants via an interlayer of mussel adhesive peptide with bioclickable properties. This study may provide a simple, efficient, and multi-functional surface strategy for improving the clinical outcomes of bio-inert medical implants. Display omitted •An upgraded mussel-inspired surface strategy were developed.•A typical AMP and the active sequence of OGP were co-clicked on PEEK osteoimplants.•The coating can defend against bacterial invasion, facilitate osteogenesis.•The optimal dual-functional coating improves osseointegration.