Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.© 2024 The Authors.