In view of the uneven distribution of regional water resources under frequent droughts and floods, based on whether the available water supply in a certain period has meet the ideal water demand of the user layer, which put forward the optimal regulation method of water resources in a year under alternating droughts and floods, and took Tuoying irrigation area as the research object, established the optimal regulation model of water resources, through the analysis of water supply capacity on the water supply side and the prediction of water resource demand on the water demand side of Tuoying irrigation area in 2030 planning level year, the long-term water resource supply and demand balance has been analyzed, and the optimal regulation scheme of water resources at the annual scale has been studied. The results have showed that the total water shortage in the planning level year was 16.92 million m³, the annual water shortage rate was 37.7% lower than that before regulation, the domestic water has been fully guaranteed, and the shortage and uneven distribution of water resources have been effectively alleviated. The research results can provide a decision-making scheme for the optimal regulation of alternating drought and flood water resources in Tuoying irrigation area, and this method can be used as a reference for optimal regulation of water resources in drought and flood prone areas.