Traditional bone replacement materials have been developed with the goal of directing the osteogenesis of osteoblastic cell lines toward differentiation and therefore achieving biomaterial-mediated osteogenesis, but the osteogenic effect has been disappointing. With advances in bone biology, it has been revealed that the local immune microenvironment has an important role in regulating the bone formation process. According to the bone immunology hypothesis, the immune system and the skeletal system are inextricably linked, with many cytokines and regulatory factors in common, and immune cells play an essential role in bone-related physiopathological processes. This review combines advances in bone immunology with biomaterial immunomodulatory properties to provide an overview of biomaterials-mediated immune responses to regulate bone regeneration, as well as methods to assess the bone immunomodulatory properties of bone biomaterials and how these strategies can be used for future bone tissue engineering applications.