The aim of this work was to develop a bioactive bone substitute with an effective antibacterial ability based on a cerium (Ce) doped glass-reinforced hydroxyapatite (GR-HA) composite. Developed composites were physicochemically characterized, using x-ray diffraction (XRD) analysis, SEM, energy dispersive x-ray spectroscopy (EDS), and flexural bending strength (FBS) tests. X-ray photoelectron spectroscopy (XPS) analysis was performed to analyze the oxidation state of Ce in the prepared doped glass. The antimicrobial activity of the composites was evaluated against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa; whether the cytocompatibility profile was assayed with human osteoblastic-like cells (Mg-63 cell line). The results revealed that the Ce inclusion in the GR-HA matrix induced the antimicrobial ability of the composite. In addition, Ce-doped materials reported an adequate biological behavior following seeding of osteoblastic populations, by inducing cell adhesion and proliferation. Developed materials were also found to enhance the expression of osteoblastic-related genes. Overall, the developed GR-HA_Ce composite is a prospective candidate to be used within the clinical scenario with a successful performance due to the effective antibacterial properties and capability of enhancing the osteoblastic cell response.