Water stress is considered one of the most critical environmental factors affecting wheat growth and productivity worldwide. So, a field experiment was conducted at the experimental farm of Shandaweel Agricultural Research Station, Sohag governorate, Egypt, during the 2017/2018 and 2018/2019 growing seasons to study the effect of the application of melatonin (30 ppm), salicylic acid (200 ppm), and mycorrhizal fungi inoculation on wheat cultivar Shandaweel 1 under three irrigation levels i.e., 5476 (I₁₀₀),4380 (I₈₀) and 3285 (I₆₀) m³ ha^-1. Results showed that decreasing irrigation water amount from 5476 to 3285 m³ ha^-1 caused a significant decrease in days to heading, days to maturity, plant height, leaf area index at 75 and days after sowing, leaf chlorophyll content, spike length, number of spikes m^-2, number of spikelets spike^-1, number of kernels spike^-1, thousand kernel weight, grain yield, biological yield, and grain carbohydrate content, while it caused a significant increase in grain protein content. Application of melatonin, salicylic acid, and mycorrhizal fungi treatments separately or in combination (salicylic acid + mycorrhizal fungi) or (melatonin + mycorrhizal fungi) reduced the negative effects of water stress in wheat as compared to the control treatment. The greatest reduction for the negative effect of water stress and the highest mean values of all studied traits were obtained with the combined application of (salicylic acid + mycorrhizal fungi) or (melatonin + mycorrhizal fungi) treatments and these combinations can play an important role in the reclamation of drought-affected land in arid and semi-arid regions.