Mimicking the hierarchical brick‐and‐mortar architecture of natural nacre provides great opportunities for the design and synthesis of multifunctional artificial materials. The crucial challenge to push nacre‐mimetic functional materials toward practical applications is to achieve ample ductility, toughness, and folding endurance with simultaneously maintaining high‐level functional properties. In this study, the microstructure of nacre‐mimetics is reformed through predesigning a 3D nanofiber network to replace conventional polymer matrices. A unique sol–gel–film transformation approach is developed to fabricate a graphene‐based artificial nacre containing a preforming 3D, interconnective, inhomogeneous poly(p‐phenylene benzobisoxazole) nanofiber network. The fabulous coupling of the extensive sliding of graphene nanoplatelets and intensive stretching of the 3D nanofiber network over a large scale enables the artificial nacre to display natural nacre‐like deformation behavior, achieving ultralarge strain‐to‐failure (close to 35%), unprecedented toughness (close to 50 MJ m−3), and fold endurance (no decrease in tensile properties after folding for 10 000 times or folding at increasing stress). The new levels of ductility, toughness, and folding endurance are integrated with outstanding thermal properties, including thermal conductivity (≈130 W m−1 K−1), thermal stability (520 °C) and nonflammability, rendering the lightweight nacre‐mimetics promising in flexible electronic devices, particularly for aerospace electronics. With a predesigned 3D interconnective nanofiber network as the matrix, graphene‐based nacre‐mimetics achieves unprecedented ductility (≈35%), toughness (≈50 MJ m−3), and folding endurance (10 000 folding cycles, folding at 20 MPa and arbitrary kneading) with simultaneous integration of high‐level functional properties (thermal conductivity, thermal stability, and nonflammability). This microstructure concept opens the door for fabricating tough, functional bioinspired materials toward practical applications.