Regionalization of food systems is a potential strategy to support environmental, economic and social sustainability. However, local preconditions need to be considered to assess the feasibility of such a transformation process. To better understand the potentials and perspectives of food self-sufficiency in urban and peri-urban areas, we determined the food self-sufficiency level (SSL) of a German metropolitan region, i.e., the percentage of the food demand that could be potentially provided on existing agricultural land. Main input parameters were actual food demand, agricultural productivity and its temporal variability and land availability. Furthermore, we considered changes in diet, food losses and land management. Based on current diets and agricultural productivity, the administrative region of Leipzig achieved a mean SSL of 94%, ranging from 77 to 116%. Additionally, an area of 26,932 ha, representing 12% of the regionally available agricultural land, was needed for commodities that are not cultivated regionally. Changes in food demand due to a diet shift to a more plant-based diet and reduced food losses would increase the SSL by 29 and 17%, respectively. A shift to organic agriculture would decrease the SSL by 34% due to lower crop yields compared with conventional production. However, a combination of organic agriculture with less food loss and a more plant-based diet would lead to a mean SSL of 95% (75–115%). Our results indicate the feasibility of food system regionalization in the study area under current and potential near future conditions. Addressing a combination of multiple dimensions, for example plant-based and healthier diets combined with reduced food loss and organic farming, is the most favorable approach to increase food self-sufficiency in urban and peri-urban areas and simultaneously provide synergies with social and environmental objectives.