The present study aimed to investigate the role of Piriformospora indica, arbuscular mycorrhiza fungi (AMF), and plant growth-promoting bacteria (PGPB) in alleviating drought stress in the HD-2967 wheat cultivar. In a completely randomized design experiment, plants were subjected to different water regimes of 75 and 35% field capacity (FC) under greenhouse conditions. Under different water regimes, microbial inoculation significantly enhanced the morphological, physico-biochemical, and ultrastructural characteristics of the wheat plants. Plants inoculated with PGPB, P. indica, and AMF showed increased shoot and root length, shoot and root biomass, leaf area, photosynthetic rate, transpiration rate, stomatal conductance, and internal CO2 as compared to uninoculated plants under all water regimes. The PGPB, P. indica, and AMF-inoculated wheat plants accumulated higher content of glycine betaine, total sugars, trehalose, proline, putrescine, spermidine, carotenoids, proteins, α-tocopherol, and a decrease in lipid peroxidation, relative membrane permeability, and lipoxygenase enzyme (LOX) activity as compared to uninoculated plants. Besides, microbes-inoculated wheat plants showed a higher level of antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) than uninoculated plants. Microbial inoculation helped wheat plants to overcome water stress-induced deficiency of macro- (Ca2+, Mg2+, and K+) and micronutrient (Cu, Mn2+, Fe, and Zn2+), and reduced damage to the cell ultrastructure (plasma membrane and chloroplasts). Comparing the potential of microbial inoculants to increase growth and nutritional, biochemical, physiological, and ultrastructural changes, the PGPB-inoculated wheat plants showed greater drought resilience followed by AMF and P. indica inoculated plants. These microbial inoculants offer a significant potential to meet the challenges of sustainable agriculture under drought conditions.