Recently, the use of silicon and bio-fertilizer has become important worldwide to improve the physicochemical characteristics of soil. Thus, they are used as an alternative approach to cope with the water-deficit stress on wheat plant. In this regard, a split-plot factorial experiment based on randomized complete block design with three replications was conducted during 2017 and 2018 at Sistan and Baluchestan Research Station, Iran. In the present study, treatments included water-deficit stress (irrigation after 60, 120, and 180 mm of evaporation from Class A pan) as the main plot, as well as the application of silicic acid (Si) foliar nutrition (0, 1, and 1.5 mM) and Nitro-Kara bio-fertilizer as sub-plots. The results represented the significant interaction effects of irrigation regimes, bio-fertilizer, and Si on 1000-grain weight and panicle number. In addition, the co-application of Nitro-Kara and Si fertilizers (1 mM) under irrigation after 120 mm evaporation led to the highest grain per panicle (44 number), which reflected a 21.36% increase compared to the control. The greatest 1000-grain weight (39.66 g) was obtained by inoculating seed with Nitro-Kara and without to apply Si fertilizer under 120 mm irrigation treatment in the first year. Further, inoculation under moderate stress (120 mm) in the second year demonstrated the highest grain yield (5,256.3 kg ha-1). Furthermore, a high chlorophyll index (57.6) was achieved when consuming 1.5 mM Si fertilizer and without Nitro Kara under 120 mm irrigation regime during the first year, which had a 20.2% enhancement compared to the control treatment. Under low irrigation conditions, the use of Nitro-Kara bio-fertilizer and Si fertilizer resulted generally in improving physiological parameters and increasing the growth and yield indices of wheat.