Drought stress is one of the most important environmental constraints that negatively affect crop growth and production worldwide. Recently, nanotechnology has increasingly been applied to improve tolerance in plants exposed to abiotic stresses such as drought. A pot experiment was conducted to examine the influence of nitric oxide donor sodium nitroprusside (SNP: 100 μM) in presence of TiO 2 nanoparticles (TiO 2 NPs: 500, 1000, and 2000 mg kg −1) on wheat seedlings under drought stress conditions. Water deficit negatively affected growth and photosynthetic parameters with simultaneous increase in activity of antioxidant enzymes. Under severe drought stress, soil-applied 2000 mg kg −1 TiO 2 NPs enhanced seedling dry weight (DW), relative water content (RWC), catalase (CAT) activity, ascorbate peroxidase (APX) activity, and proline content. Moreover, 2000 mg kg −1 TiO 2 NPs enhanced total chlorophyll (total Chl), carotenoids (Car), stomatal conductance (gs), and transpiration (E) under severe drought stress. However, addition of 100 μM SNP in presence of 2000 mg kg −1 TiO 2 NPs significantly increased seedling length (SL), superoxide dismutase (SOD) activity, total soluble proteins, net photosynthetic rate (Pn), and intercellular CO 2 concentration (Ci). The aforementioned treatment also significantly reduced hydrogen peroxide (H 2 O 2) and malondialdehyde (MDA) contents under severe drought stress. Our results suggest that foliar application of SNP in the presence of TiO 2 NPs can protect wheat seedlings against drought-induced oxidative damage.