Silicone is the primary implant material used in plastic surgery; however, it exhibits some inherent disadvantages. For instance, it can cause delayed seroma, breast implant-associated anaplastic large cell lymphoma, and capsular contracture, which are closely related to the type of implant surface. Biomaterial surface modification techniques are continuously being improved for application in many fields. Herein, conditions for oxygen (O2) plasma treatment on various surface types of peri-silicone implants were optimized. Following optimal treatment, surface hydrophilicity, protein adsorption, bacterial adhesion, cell viability and proliferation, changes in implant shell mechanical properties, and in vivo tissue response were examined. Hydrophobicity decreased following O2 plasma treatment. Bacterial adhesion and protein adsorption were significantly inhibited, and mechanical properties were improved. There was no topographic change on the implant surface. In vitro cells were evenly distributed on the O2 plasmatreated surface, and in vivo analysis confirmed a decrease in capsule thickness, collagen fiber composition, number of inflammatory cells, and TGF-β1 and α-SMA expression. Additionally, reduced activation of cytokines related to macrophage and T-cell responses was observed. O2 plasma surface treatment, under optimal conditions, is a simple and effective method with potential clinical applications for attenuating excessive capsule formation and the immune response.