Discoveries of two-dimensional (2D) materials, exemplified by the recent entry of MXene, have ushered in a new era of multifunctional materials for applications from electronics to biomedical sensors due to their superior combination of mechanical, chemical, and electrical properties. MXene, for example, can be designed for specialized applications using a plethora of element combinations and surface termination layers, making them attractive for highly optimized multifunctional composites. Although multiple critical engineering applications demand that such composites balance specialized functions with mechanical demands, the current knowledge of the mechanical performance and optimized traits necessary for such composite design is severely limited. In response to this pressing need, this paper critically reviews structure–function connections for highly mineralized 2D natural composites, such as nacre and exoskeletal of windowpane oysters, to extract fundamental bioinspired design principles that provide pathways for multifunctional 2D-based engineered systems. This paper highlights key bioinspired design features, including controlling flake geometry, enhancing interface interlocks, and utilizing polymer interphases, to address the limitations of the current design. Challenges in processing, such as flake size control and incorporating interlocking mechanisms of tablet stitching and nanotube forest, are discussed along with alternative potential solutions, such as roughened interfaces and surface waviness. Finally, this paper discusses future perspectives and opportunities, including bridging the gap between theory and practice with multiscale modeling and machine learning design approaches. Overall, this review underscores the potential of bioinspired design for engineered 2D composites while acknowledging the complexities involved and providing valuable insights for researchers and engineers in this rapidly evolving field.