The hierarchical interfacial architecture of nacre inspires the fabrication of novel high performance graphene‐based nanocomposites. Graphene has great promise for applications in aerospace and especially for flexible electronic devices, etc., due to its remarkable mechanical and electrical properties. Thus, it is significant to summarize the role of interface interactions in the construction of nacre‐inspired graphene‐based nanocomposites, which is the distinctive characteristic and important scientific progress of the review. This review first makes a comparison for the interfacial architecture of above biological materials and finds inspiration from nacre to design the interface in graphene‐based nanocomposites, which contains single interface interaction, synergistic interface interactions, and synergistic building blocks. Then, the focus is attached to the effect of different interfacial design strategies on the mechanical and electrical properties of state‐of‐the‐art GO‐based artificial nacres (GANs), including 1D fibers, 2D films, and 3D bulk materials. Additionally, the multifunctional GANs with such functions as fatigue resistance, fire retardant property, and smart nanogating, etc. are also discussed. Moreover, some potential applications and corresponding challenges and solutions of GANs are detailedly summarized. Finally, from the views of theoretical simulation and experimental research, a perspective on the roadmap of GANs in the future is also proposed.