Crop productivity worldwide is being hampered by salt stress. Nanotechnology and its applications in agriculture are noteworthy and fruitful. The current work investigates the potential significance of TiO2 NPs in alleviating salt stress in wheat cultivars. TiO2 NPs were prepared by green synthesis; their characterizations were carried out by UV–visible spectroscopy, SEM, and EDX. In the greenhouse control condition, different concentrations of salt (NaCl) with and without TiO2 NPs were administered to wheat crops. Plants treated with TiO2 NPs showed an enhanced germination rate, morphological, and metabolic profiling with and without salt stress. Different concentrations of TiO2 NPs (25, 50, 75, and 100 µg/mL) and salt solutions (NaCl 50, 100, and 150 mM) were used. TiO2 NP concentrations of 25 µg/mL and 50 µg/mL improved the germination attributes, physio-morphic parameters: plant length, the fresh and dry weight of plants, the number of leaves, the leaf area, the RWC, the MSI, and different chlorophyll contents at all saline conditions. These two concentrations also enhanced the biochemical attributes: free amino acids, soluble sugar content, proline content, SOD, and POD, of wheat varieties at all salinity levels. Wheat subjected to salt stress responded best to the application of TiO2 NPs at a concentration of 50 µg/mL. However, the highest concentrations (75 and 100 µg/mL) of TiO2 NPs showed detrimental effects on germination, agronomic, physiological, and biochemical attributes, and caused stress in both wheat varieties (Pirsabak-05 and NARC-09) under control and saline conditions. The outcomes of the current research work are notable, and NPs with such capabilities may be a useful supply of fertilizer in the agricultural industry.