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Introduction. Modern challenges and threats to the development of the Russian agro-food complex determine the search for new growth sources of the complex, the strengthening of orientation towards the formation of a balanced functional and sectoral structure. The relevance of the regional aspect of research and substantiation of structural changes in the agro-food complex is associated with a deep socio-economic, natural-climatic and socio-cultural differentiation of the country’s regions. Theoretical analysis. Changing the role of regions in solving food security problems and providing the population with quality food is a global trend. The rupture of global food chains as a result of the COVID-19 pandemic and the sanctions confrontation strengthens the influence of local producers on the food market, suggests the need to form a multilevel agro-food complex of the country. Structural changes in the agro-food complex of Russia have their own characteristics associated with the heterogeneity of its spatial development. Empirical analysis. The accelerated growth of the agricultural sector of Saratov region economy due to the concentration on the production of a limited group of agricultural products (cereals and oilseeds, sugar) has been revealed. The regional food market segments, which have a surplus and shortage of products, are determined. It is substantiated that current trends extrapolation in the development of the regional agro-food complex preserves its unbalanced structure and further growth in the share of raw materials and primary processing products, while reducing the share of deep processing products. Results. Adaptation to new risks and threats is associated with an increasing trend towards the localization of production and supply of agricultural products and food. The priority areas for the development of the regional food system should be the diversification of agro-food production, local food chains formation with deep processing of agricultural raw materials, and the intensification of interregional exchange.