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 (H<inf>2</inf>O<inf>2</inf>) and malondialdehyde (MDA), confirming oxidative damage. Saponin modulated these effects depending on concentration and genotype. Notably, 5% saponin under SWS caused the greatest H<inf>2</inf>O<inf>2</inf> 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.