The long-term strategy for the development of the grain complex of the Russian Federation provides the innovative formation of grain clusters, that covers the entire value chain: from production to export of grain and its processed products. Grain-oriented clusters constitute highly complex socio-economic, organizational and biotechnological systems in which biological factors determine their effectiveness to a decisive extent. The aim of the study is to develop a bio-economic approach that promotes the application of biological knowledge to improve the efficiency and competitiveness of the grain complex. The study used methodological approaches: system-synergetic, cluster, bio-economic and global. The application of these approaches made it possible to identify “gaps”, a sharp weakening of natural biological positive feedbacks in the main grain-producing regions between crop production and animal husbandry, plants and soil biota. Moreover, a definition of the concept “bioeconomics” was formulated in the narrow sense. In addition, the need to implement the circular bioeconomics was justified in relation to the grain complex. Finally, the need to develop bioeconomics was substantiated in the cluster format.