Drought stress, namely water-deficit stress, is a major constraint on plant growth and productivity, particularly in rainfed agricultural systems. Saponins, a class of plant-derived secondary metabolites within the terpenoid group, are not directly involved in essential physiological processes but may contribute to plant responses to abiotic stress. However, their role in early-stage drought stress tolerance and the underlying physiological and biochemical mechanisms remains insufficiently understood. This study investigated the effects of foliar applied saponin (0%, 1%, 3%, and 5%) on two wheat cultivars with contrasting drought tolerance, Dağdaş 94 (tolerant) and Aldane (sensitive), under four irrigation regimes: no stress (NWS), light (LWS, 25%), moderate (MWS, 50%), and severe water stress (SWS, 75%). The greenhouse experiment followed a completely randomized design with three replications. Saponin had a significant effect on root length, while shoot growth in Dağdaş 94 improved with 1% saponin under NWS but was inhibited by 5% under SWS. Biomass production was generally unaffected by genotype or treatment, although the lowest values occurred at 3% saponin. Water use efficiency (WUE) increased with stress severity but was not influenced by saponin. Water stress substantially elevated hydrogen peroxide (H2O2) and malondialdehyde (MDA), confirming oxidative damage. Saponin modulated these effects depending on concentration and genotype. Notably, 5% saponin under SWS caused the greatest H2O2 and MDA accumulation in Aldane, while 1–3% saponin reduced MDA under MWS in both cultivars. Antioxidant enzyme activities (SOD, POD, APX) generally increased with stress and saponin, though 3% saponin limited POD induction in Dağdaş 94. Overall, moderate saponin concentrations (1–3%) improved antioxidant responses and reduced oxidative damage under water stress, highlighting its potential as a bioactive treatment to enhance drought resilience in wheat.