The largest possible planar surfaces are highly sought for two-dimensional (2D) Au single-crystals applicable in catalysis, biomedicine, electronics, sensing, and optics. However, conventional chemical methods of synthesis are currently limited to planar area of 10⁴ μm². Here, the trans-scale and 2D growth of Au single-crystals is successfully achieved in a “kinetically controlled” pathway, taking advantage from natural fibrous proteins with different amino sequences and supramolecular architectures. It was found that silk fibroin (SF) has a uniquely suited amino sequence and supramolecular assembly ability to fulfill this task, enabling mild reducing ability and strong capping effects. By the synergetic aid of Cl^– ions, 2D Au single-crystals were synthesized with an unprecedented lateral dimension exceeding 2 mm, yet with atomically smooth surfaces. When growing nanotips on their large planar surfaces, these 2D Au crystals stand as ideal platforms for single-molecule sensing (e.g., surface enhanced Raman scattering) and catalysis. The combination of sensing and catalysis further enabled the Au crystals to serve as the probes for many reactions of significance in bionanotechnology, medicine, and environments.