Regenerative medicine leverages the innate potential of the human body to efficiently repair and regenerate damaged tissues using engineered biomaterials. By designing responsive biomaterials with the appropriate biophysical and biochemical characteristics, cellular response can be modulated to direct tissue healing. Recently, inorganic biomaterials have been shown to regulate cellular responses including cell-cell and cell-matrix interactions. Moreover, ions released from these mineral-based biomaterials play a vital role in defining cell identity, as well as driving tissue-specific functions. The intrinsic properties of inorganic biomaterials, such as the release of bioactive ions (e.g., Ca, Mg, Sr, Si, B, Fe, Cu, Zn, Cr, Co, Mo, Mn, Au, Ag, V, Eu, and La), can be leveraged to induce phenotypic changes in cells or modulate the immune microenvironment to direct tissue healing and regeneration. Biophysical characteristics of biomaterials, such as topography, charge, size, electrostatic interactions, and stiffness can be modulated by addition of inorganic micro- and nanoparticles to polymeric networks have also been shown to play an important role in their biological response. In this Review, we discuss the recent emergence of inorganic biomaterials to harness the innate regenerative potential of the body. Specifically, we will discuss various biophysical or biochemical effects of inorganic-based materials in directing cellular response for regenerative medicine applications.