Abstract: The Ningdong Coalfield is located in the arid and semi-arid region of northwest China, which is one of the 14 approved large-scale coal bases with a reserve of over 100 million tons in China. Currently, it faces challenges such as a large volume of highly-mineralized mine water, mature but costly treatment technology, and a low comprehensive utilization rate. To achieve the low-cost efficient reinjection and storage of highly-mineralized mine water in the Ningdong Coalfield and to protect the hydrological and ecological environment, this study, based on the typical characteristics of high mineralization in the mine water of 13 coal mines in the Ningdong coalfield, proposes a technical approach for the reinjection and storage of highly-mineralized mine water in depleted petroleum reservoirs in the coal and oil resources overlapping area. This approach utilizes the valuable unconventional water resource by making use of the pore-fracture dual structure and water storage space in the depleted petroleum reservoirs, the initial reservoir pressure vacuum during the shutdown of the oilfield, and the low-cost disposal of highly-mineralized mine water after resource utilization. The study systematically elaborates on the selection of depleted petroleum reservoirs, reinjection processes, water storage potential, pre-treatment water quality requirements, and the feasibility analysis of the environment. It also outlines prospects for fundamental theoretical research, legal regulations, policies, and real-time monitoring and control. The results indicate the feasibility of the proposed reinjection and storage technology in depleted petroleum reservoirs, which can achieve the low-cost efficient treatment of highly-mineralized mine water in the Ningdong Coalfield. “How to finely characterize the water injection seepage process” is identified as a bottleneck issue in the reinjection treatment technology. In essence, it involves the evolution mechanism of water injection and seepage in the pore-fracture scale of the depleted petroleum reservoir under the coupled chemical action of highly-mineralized mine water and sandstone. Furthermore, there is an urgent need for improvement in related legal regulations, policies, and real-time monitoring and control to ensure the smooth implementation of the reinjection and storage technology in depleted petroleum reservoirs. This study aims to provide new insights into efficiently reinjecting and storing highly-mineralized mine water and to offer references for the protection of secondary water resources in the development of coal, oil, and gas resources.