Biological materials have evolved over millions of years and are often found as complex composites with superior properties compared to their relatively weak original constituents. Hard biomaterials such as nacre, bone, and dentin have intrigued researchers for decades for their high stiffness and toughness, multifunctionality, and self-healing capabilities. Challenges lie in identifying nature’s mechanisms behind imparting such properties and her pathways in fabricating these composites. The route frequently acquired by nature is embedding submicron- or nano-sized mineral particles in protein matrix in a well-organized hierarchical arrangement. The key here is the formation of large amount of precisely and carefully designed organic–inorganic interfaces and synergy of mechanisms acting over multiple scales to distribute loads and damage, dissipate energy, and resist change in properties owing to events such as cracking. An important aspect to focus on is the chemo-mechanics of the organic–inorganic interfaces and its correlation with overall mechanical behavior of materials. This review focuses on presenting an overview of the past work and currently ongoing work done on this aspect. Analyses focuses on understanding role played by the interfacial mechanics on overall mechanical strength of hard biomaterials. Specific attention is given to synergy between experiments and modeling at the nanoscale to understand the hard biomaterial biomechanics.