Biomacromolecules, the first components of bioactive substances in traditional Chinese medicines (TCM) have wide bioactivity-related efficacy but have not yet been fully appreciated compared to small molecule components. The present review brings a novel and systemic point of view to deepen the understanding of the pharmacodynamic material basis of TCM based on biomacromolecules (polysaccharides, proteins and nucleic acids). Biomacromolecules have been, are and will have considerable roles in the efficacy of Chinese medicine, as evidenced by the number of biological activities related to traditional clinical efficacy. The direct and indirect mechanisms of biomacromolecules are further accounted for in a variety of neurotransmitters, hormones, and immune substances to maintain immune function in both sensitive and stable equilibrium. The biological functions of biomacromolecules have been elaborated on in regard to their roles in the process of plant growth and development to the relationship between primary metabolism and secondary metabolism and to the indispensable role of polysaccharides, proteins, and nucleic acids in the quality formation of TCM. Understanding the functional properties and mechanisms of biological macromolecules will help to demystify the drug properties and health benefits of TCM.