Soil salinization and sodication adversely affect soil fertility and agricultural output, particularly in arid and semi-arid regions. This research sought to assess the effects of soil application of nano-gypsum (NG), inoculation with salt-tolerant plant growth-promoting bacteria (PGPB), and foliar application of nano-calcium oxide (NCaO), nano-zinc oxide (NZnO), and nano-silica (NSiO2) on wheat cultivated in saline-sodic soil. The results demonstrated significant enhancements in various growth parameters of wheat, including pigments, proline acid (PA), total soluble sugars (TSS), ascorbic acid (ASA), biomass yield, and wheat grain production. The levels of essential nutrients in the wheat increased as a result of applying NG, PGPB, and the foliar application of nanoparticles, with foliar application of NZnO exhibiting the most significant effect, followed by NSiO2. Additionally, the concentration of Na+ in the wheat tissues was reduced. In conclusion, the combined application of NG, PGPB, and foliar nanoparticles markedly improved the growth and productivity of wheat in saline-sodic conditions, particularly through the foliar application of NZnO and NSiO2, as well as soil application of NG and subsequent inoculation with PGPB.