Inorganic protein hybrid materials (IPHMs) due to editable structure present unrivalled potential at the intersection of synthetic biology and materials science. The synthesis of IPHMs with a high degree of biosafety from bioactive units represents a shift in material design and synthesis. This paper focuses on a review of the structural basis and design principles of proteins for the synthesis of IPHMs with specific physical and chemical functions. It also provides a valuable reference for the design of emerging IPHMs through the conformational relationship of the IPHMs, which extends the potential applications of IPHMs. In addition, the construction strategy of the reaction system for the synthesis of hybrid materials is analyzed from the perspective of synthetic biology. The possibility of engineering and batch synthesis of IPHMs is discussed. Based on the physicochemical properties of different hybrid materials and the applied-oriented research on biomedical optical imaging and multimodal therapy, the idea of synthesis of in situ hybrid materials is proposed. Ultimately, the trends and challenges of synthetic biology for IPHMs are speculated in detail.