<p>One of the enduring goals in structural materials engineering is the development of lightweight materials that combine high strength with exceptional toughness. Natural composites such as nacre have long served as a source of inspiration, as their outstanding mechanical performance stems not only from their intricate hierarchical architecture but also from the vital role of interfaces in controlling deformation and resisting crack propagation. Here, we present a computational model of a three-dimensional (3D) staggered nacre-mimicking nanocomposite and report parametric studies that investigate the roles of interfacial properties (strength and toughness) in controling the bulk properties and failure behaviors under both tensile and compressive loading conditions. Our findings reveal that under tensile loading, the bulk properties are primarily controlled by the surface normal interfacial properties, and composite failure exhibits normal-mode fracture patterns. In contrast, under compressive loading, interfacial shear properties predominantly control the bulk properties, and composite failure patterns follow shear-mode fracture behavior. These findings provide specific design guidelines for tailoring the interfacial properties of nacre-like bioinspired structural composites under different loading conditions.</p>