Like other deltas in the world, the delta of the Amu Darya river is a very dynamic natural system that reflects all the processes and developments that occur in a river basin. Water and terrestrial ecosystems of the Amu Darya delta and the Southern Aral Region provide valuable services derived from natural systems and maintain the welfare of the local population, who are strongly affected by the Aral Sea environmental disaster and land salinization, degradation, and desertification. The importance of the deltaic systems as an additional source of income and a buffer against economic hardships increased after the Aral Sea desiccation and social and economic transformations. This case study contains an analytical review of the issues concerning the restoration of saline soils and agricultural policy in support of food security using the example of the Amu Darya delta in Uzbekistan. The studied area is located in the northern part of the delta between 42°30'N and 44°00'N in North Karakalpakstan (the Pre-Aral region) in Uzbekistan. It includes agricultural land (irrigated land, pastures, and lake systems), which make a major contribution to food security, as well as water ecosystems (wetlands) that provide valuable services derived from natural systems. Cultivated land and water ecosystems in the delta depend entirely on the river water flow and collector/drainage runoff and are extremely susceptible to reduced flow caused by climate change and the increase in the number of climate extremes. This case study focuses on two stakeholder groups: (i) local stakeholders such as water users/consumers, agricultural producers, rural citizens' meetings, fishermen, dehkans (peasants) and other vulnerable groups; and (ii) national and regional stakeholders–for example, key government institutions, ministries and agencies, regional and district authorities (khokimiats), basin administrations of irrigation systems (BAIS) under the Ministry of Agriculture and Water Resources and their branches, and organizations responsible for the development and implementation of targeted programs, strategies, and environmental management plans. This case study will demonstrate how the productivity of salt-affected irrigated lands can be improved and the services of water ecosystems in the Amu Darya delta in Uzbekistan can be sustained to support food security in the long term in the context of climate challenges. The following two food policy options are recommended [1]: (i) sustaining and maintaining food self-sufficiency and balances between food consumption and production by increasing production output to meet projected food shortages; and (ii) increasing production of food products in subsectors where Uzbekistan possesses a comparative advantage with the aim of substantially increasing of their export. To achieve these targets, it is necessary to implement a range of interventions and measures aimed at further development of reforms and incentives in land and water use, mobilization of resources, and strengthening of institutional capacity along with the implementation of new forms and methods of planning, knowledge management, and awareness- raising among all stakeholders to disseminate innovations and replicate best agrotechnologies on a wider scale. These interventions should be extremely cautious; technically, economically, and environmentally acceptable; and socially relevant in order to achieve sustainable environmental and economic benefits and improve livelihood and food security.