As the population ages worldwide, the importance of maintaining the metabolism of the skeletal system becomes increasingly important. The skeleton is the core of the locomotor and oral structure. Moreover, infection control is an essential part of orthopedic and oral surgery. This paper investigates new bone substitutes fabricated by the ionic substitution method leading to octacalcium phosphate (OCP) with excellent contact antibacterial ability, biocompatibility, and bone replacement. To improve the functionality of OCP-based materials as a bone substitute, we introduce a novel OCP block fabrication method based on the dissolution–precipitation method, study the factors that induce OCP in solution, and propose a robust method for cation substitution in the OCP unit lattice named the ionic insertion method. We then fabricate Ag-substituted OCP (OCP–Ag) blocks using this method and evaluate their antibacterial activity in vivo. These techniques will contribute to new-generation medical services and improve the quality of life of individuals requiring implants.