A pot study was conducted to explore the effectiveness of zinc oxide nanoparticles (ZnO NPs) foliar exposure on growth and development of wheat, zinc (Zn) and cadmium (Cd) uptake in Cd-contaminated soil under various moisture conditions. Four different levels (0, 25, 50, 100 mg/L) of these NPs were foliar-applied at different time periods during the growth of wheat. Two soil moisture regimes (70% and 35% of water holding capacity) were maintained from 6 weeks of germination till plant harvesting. The results revealed that the growth of wheat increased with ZnO NPs treatments. The best results were found in 100 mg/L ZnO NPs under normal moisture level. The lowest Cd and highest Zn concentrations were also examined when 100 mg/L NPs were applied without water deficit stress. In grain, Cd concentrations decreased by 26%, 81% and 87% in normal moisture while in water deficit conditions, the Cd concentrations decreased by 35%, 66% and 81% compared to control treatment when ZnO NPs were used at 25, 50 and 100 mg/L. The foliar exposure of ZnO NPs boosted up the leaf chlorophyll contents and also decreased the oxidative stress and enhanced the leaf superoxide dismutase and peroxidase activities than the control. It can be suggested that foliar use of ZnO NPs might be an efficient way for increasing wheat growth and yield with maximum Zn and minimum Cd contents under drought stress while decreasing the chances of NPs movement to other environmental compartment which may be possible in soil applied NPs. •Cadmium (Cd) and water stress negatively affected shoot, roots and grain yield of wheat.•Foliar application of zinc oxide nanoparticles (ZnO NPs) improved the growth under stress.•Foliar ZnO NPs improved chlorophyll contents and minimized oxidative stress in shoots.•Foliar ZnO NPs increased Zn and decreased Cd contents in wheat grains under Cd and water deficient stress.