Magnesium phosphate-based bone cements (MPBCs) have been widely applied in orthopedic and dental fields owing to their excellent self-setting ability and high strength. However, their lack of macroporosity and poor drug release properties restrict their use. In this study, we incorporated various degrees of cross-linking of gelatine microspheres (GM) into MPBC and improved the physicochemical and biocompatible properties, biodegradation and drug release behaviour of the composites. Diclofenac sodium (DS) was utilized as a model drug. Through experiments and observations, we found that the GM induced an adjustable setting time (12 min-16 min), high compression strength (23 MPa-58 MPa), abundant macropores (30.2%-37.8%) and sustained DS release with the double exponential biphasic kinetic model (more than 2 months) into the MPBC composites. Moreover, the sustained release of magnesium and calcium ions had a synergistic effect with GM on the proliferation, osteogenesis differentiation, mineralization ability and gene expression (COL I, OPN, and Runx2) of MC3T3-E1 cells. Subcutaneous implantation and histological analyses indicated that the MPBC-GM composites activated angiogenesis without inducing severe inflammatory reactions. In brief, we prepared biocompatible MPBC composites with adjustable physicochemical properties, formation of macropores, degradation and drug release behaviour. (C) 2021 The Author(s). Published by Elsevier Ltd.