Drought is one of the most important abiotic stress factors that limit plant growth and productivity but studies documenting how drought stress regulates boiling soluble antioxidants in cultivars differing in drought tolerance has not been critically evaluated. In this study, we analysed the indices of oxidative stress {H2O2, O2 .-, Membrane Injury Index (MII), Membrane Stability Index (MSI) and lipid peroxidation (MDA)} and activities of ROS-scavenging boiling soluble antioxidant enzymes in caryopses of sensitive and tolerant cultivars of wheat at different stages of development. Water Content (WC) recorded a decline in both the sensitive cvs. PBW 621 and 343 while in tolerant cvs. PBW 175 and 527, it remained unresponsive to drought conditions at 35 DPA. Oxidative stress indicators increased in a cultivar genotype and developmental stage dependent manner under stress. MII increased in all the cultivars under stress conditions in a stage specific manner. Basal activities of various boiling soluble antioxidants like BsMDAR, BsCAT, BsAPX, and BsGR were significantly higher in caryopses of tolerant cvs. PBW 527 and 175 as compared to sensitive cvs.PBW 343 and 621. Activities of BsMDAR, BsGST, BsPDI, BsGR, BsSOD, BsGPX, and BsAPX were induced or increased in the tolerant cvs.PBW 527 and 175 under drought stress while nil or decreased activities were detected in the sensitive cvs. PBW 343 and 621 at different developmental stages. Based upon our findings, it can be inferred that tolerant cultivars may have more biochemical capacity to perform biological antioxidative reactions to combat drought-induced oxidative stress.