Regenerable, high-efficiency salt sorption materials are highly desirable for water treatment. Here, a thermoresponsive, amphoteric metal-organic framework (MOF) material is reported that can adsorb multiple salts from saline water at room temperature and effectively release the adsorbed salts into water at elevated temperature (e.g., 80 °C). The amphoteric MOF, integrated with both cation-binding carboxylic groups and anion-binding tertiary amine groups, is synthesized by introducing a polymer with tertiary amine groups into the cavities of a water-stable MOF such as MIL-121 with carboxylic groups inside its frameworks. The amphoterized MIL-121 exhibits excellent salt adsorption properties, showing stable adsorption-desorption cycling performances and high LiCl, NaCl, MgCl , and CaCl adsorption capacities of 0.56, 0.92, 0.25, and 0.39 mmol g , respectively. This work provides a novel, effective strategy for synthesizing new-generation, environmental-friendly, and responsive salt adsorption materials for efficient water desalination and purification.