The paper describes the new phenomenon called Ion-Exchange Isothermal Supersaturation (IXISS). This effect is observed for a number of ion-exchange systems, where frontal or reverse frontal separation is accompanied by the formation of stable supersaturated solutions of slightly soluble substances in the interstitial space of ion-exchange columns. After leaving the column a supersaturated solution crystallizes spontaneously, which allows for designing practically ideal ion-exchange process where a crystalline product is obtained right after the ion-exchange purification cycle. The paper comprises results on experimental investigation of IXISS of amino acids (e.g., such as glutamic, aspartic and some others), calcium and magnesium salts (sulfates and carbonates), and some other substances. The mechanisms of stabilization of supersaturated amino acid solutions in the interstitial space is proposed and confirmed experimentally. Methods for identification of substances exhibiting the IXISS effect and practical application of the IXISS phenomenon for separation and ion-exchange synthesis of substances and some other problems are discussed.