The yield of crops is threatened significantly by environmental stresses in various parts of the world. So, the non-essential element silicon and seed priming with mycorrhiza and growth-promoting bacteria are known to improve plant fitness by alleviating the effects of environmental stress, particularly in crops. However, the potential role of the integrated application and their possible role in the exceptional tolerance of this variety of wheat to salinity have not been investigated. This project was designed to assess the potential role of silicon nanoparticles (Si-NPs) and bio-fertilizers in increasing wheat's tolerance to salinity stress by assessing antioxidant activity. The experiment was carried out as a factorial based on a randomized complete block design in greenhouse conditions. The experimental factors consisted of different levels of salt (0, 35, 70, and 105 mM), Si-NPs (0, 30, and 60 mg/L), and bio-fertilizers (control, mycorrhizal fungi, Flavobacterium, and Pseudomonas strain 18,798 bacteria, application of both bacteria and fungi). The results showed that, under salinity stress, the selected bio-fertilizers and Si-NPs enhanced plant leaf water potential (94.4%), soluble protein (58.61%), soluble sugar (57.54%), catalase (79%), peroxidase (95.87%), and polyphenol oxidase (90.93%) parameters. Both single and dual bio-fertilizers and Si-NPs application improved physiological parameters by stomatal conductance, electrical conductivity, electrolytic leakage and proline. Also, the highest grain yield and lowest malondialdehyde, hydrogen peroxide content were obtained in the combined application of bio-fertilizers and Si-NPs application (60 mg/L) under non-salinity stress. Therefore, obtained results indicated that Si-NPs and bio-fertilizers can improve wheat grain yield under salinity stress conditions by improving the physiological and biochemical traits.