Soil salinity is one of the most significant environmental constraints to global agricultural productivity. To meet the nutritional needs of the growing population, cereals such as wheat, which are essential for dietary products but also sensitive to salinity, must be improved to be either more resilient or less susceptible to salt stress. The main objective of this study was to examine the responses of advanced mutant lines to salt stress. Five-advanced mutant wheat lines, which were previously found to be drought tolerant, were grown under 150 mM NaCl stress conditions to see how they responded to salt stress conditions. They were generated via 200 Gy gamma-ray applications to the Sagittario commercial cultivar. The results show that the content of thiobarbituric acid-reactive substances (TBARS), chlorophyll, and electrolyte leakage % did not change significantly. Mutant lines showed higher antioxidant defense system parameters (SOD, CAT, POX, and GR). Similarly, the amount of proline involved in intracellular homeostasis was higher in all mutants. Under saline stress, the expression of Triticum aestivum Salt Overly Sensitive 1 (TaSOS1) increased in all mutant lines, the expression of Triticum aestivum High-Affinity Potassium ion Transporter 2;1 (TaHKT2;1) increased in all except in mutant line 5, and the expression of Triticum aestivum Sodium ion / Hydrogen ion vacuolar antiporter (TaNa⁺/H⁺ vacuolar antiporter) increased in all except in mutant line 3. Synergetic interaction in the expression of the genes involved in signal transduction resulted in more intracellular K⁺. Overall, these results suggest that mutants’ responses to salinity stress is related to an ability to accumulate K⁺ in cells with synergetic expressional regulation of TaHKT2;1, TaNa⁺/H⁺ vacuolar antiporter, and TaSOS1 genes, in addition to responses of antioxidant enzyme activities and the accumulation of proline.