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Background In recent years, bioactive bioceramics such as bioglass and hydroxyapatite (HA) have been introduced as a remarkable development in the field of medicine due to their bio-adaptability, non-toxicity, and persistence, in vivo. They have many potential applications in the repair of bone defects and hence they have attracted significant interest from scholars. Objectives The aim of this study was to synthesize inorganic matrix CuO-based bioglasses and evaluate their antibacterial activity against aerobic bacterial infections in bone implants. Methods Nano-composite samples of silica-based bioactive glass, 60S BG with nano-powder CuO, were synthesized using the sol-gel method and then assessed with regard to their antibacterial properties against Staphylococcus aureus using well diffusion agar. The samples included BG58S (58%SiO2, 36%CaO, 6%P2O5), BG/10CuO (58%SiO2, 26%CaO, 6%P2O5, 10%CuO), and BG/20CuO (48%SiO2, 26%CaO, 6%P2O5, 20%CuO). To evaluate their bioactivity, the prepared samples of BG/20CuO, BG/10CuO, and BG58S were immersed in simulated body fluids (SBF). The surface morphology and structure of the samples before and after immersion in the SBF were characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR), respectively. Then, the BG/20CuO and BG/10CuO samples were loaded in clindamycin, an antibiotic widely used in the treatment of osteomyelitis, and their release profiles were studied in phosphate buffer solution. Results It was observed that the growth inhibition zone increased through clindamycin release due to the increasing CuO percentage in the nanocomposite of bioactive glass. The bioactivity of the nanocomposite/bioglass with CuO was superior to that of bioglass alone. In this study, the BG/20CuO sample showed a sustained release of clindamycin, which is sufficient for a drug delivery system. Conclusions Increasing the Cu nanoparticles in bioactive glass samples leads to the release of Cu2+, which has a positive effect on the antibacterial mechanism, as well as decreasing the cultured Staphylococcus colonies found on the bioglasses. Therefore, it seems that the nanocomposite/bioglass of CuO is a promising option for aerobic bacterial inhibitor systems in common bone implant infections.