Bone infections are a challenging problem as they may cause a permanent patient disability and even death. Additionally, their relapse rate is relatively high. The implantation of a local drug delivery system can be an effective way to fight bone infections. In this study, we present the process of surface bioactivation and immobilization of nanoparticles loaded with drugs. Our aim was to improve osseointegration of the ZrO2 surface by coating it with a bioactive layer containing poly(L-lactide-co-glycolide)(PLGA) nanoparticles (NPs) loaded with antibacterial drugs (gentamicin and bacitracin) using a biomimetic precipitation method. The ZrO2 substrates were prepared via pressing and sintering. The CaP-coating was obtained by immersing the substrates in ten-times concentrated simulated body fluid (10×SBF). NPs were prepared by the double emulsion method and the drug loading in NPs was assessed. Thus obtained NPs were applied on bioactivated ceramic substrates by the drop-casting method or by introducing them in the 10×SBF solution during the bioactivation process. The NPs were visualized using scanning electron microscopy (SEM). The NPs size and the Zeta potential were measured using dynamic light scattering (DLS) method. The microstructure of the coating and the efficiency of the NPs incorporation were tested by SEM. In this study, we proved the presented process to be an effective way to obtain biomaterials that could be used as drug delivery systems to treat bone infections in the future.