Biomacromolecules refer to the substances such as DNA, proteins, polysaccharides, etc. in living organisms, which are essential for the normal life activities of organisms. De novo synthesis and design techniques have high degree of freedom and simple precursors in the synthesis and structural design of biomacromolecules, enabling new design and efficient synthesis of biomacromolecules for specific research purposes. Recently, de novo synthesis and design techniques have begun to receive attention in the fields of artificial gene combination, novel protein drug design, glycoconjugate synthesis, etc. Based on the de novo synthesis and design of biomacromolecules, the newly designed DNA or novel gene expression products, as well as glycosylation or glycoconjugates with recognition functions, can be targeted prepared. Simultaneously, the techniques will greatly advance biologically active substances such as cytokine mimics, gene therapy delivery vehicles, providing a new solution for the construction of artificial biological systems and the treatment of rare diseases. This paper reviews the de novo synthesis and design of DNA, protein and polysaccharides, expounds the related methods and applications, and finally summarizes the relationship between three kinds of substances.