We are developing a comprehensive de novo chemical protein synthesis methodology to create structurally unrestricted proteins capable of transcending the constraints of biology. This methodology is centered on the widely adopted peptide hydrazide ligation we pioneered—an approach enabling flexible, high-yield, and cost-effective assembly of multiple peptide segments into full-length proteins via a convergent strategy. Three technical innovations steadily augment this hydrazide-centric methodology: 1) temporary structural scaffolds to expedite protein folding; 2) artificial miniature ligases to accelerate interdomain assembly; 3) protein chemosynthesis robots to enable AI-driven automation. Leveraging this methodology, we design and generate an expanding repertoire of synthetic—and often “beyond-biology”—proteins across unbounded chemical space: either to discover and target cryptic, therapeutically rewirable interprotein interactions (e.g., via molecular glues) for disease intervention, or to develop artificial protein products (protein/peptide drugs, enzymes, and biomaterials) through AI-powered generative molecular design.