The phytopathogenic basidiomycetous fungus, Rhizoctonia solani, has a wide range of host plants including members of the family Poaceae, causing damping-off and root rot diseases. In this study, we biosynthesized spherical-shaped silicon dioxide nanoparticles (SiO2 NPs; sized between 9.92 and 19.8 nm) using saffron extract and introduced them as a potential alternative therapeutic solution to protect wheat seedlings against R. solani. SiO2 NPs showed strong dosedependent fungistatic activity on R. solani, and significantly reduced mycelial radial growth (up to 100% growth reduction), mycelium fresh and dry weight, and pre-, post-emergence damping-off, and root rot severities. Moreover, the impact of SiO2 NPs on the growth of wheat seedlings and their potential mechanism (s) for disease suppression was deciphered. SiO2 NPs application also improved the germination, vegetative growth, and vigor indexes of infected wheat seedlings which indicates no phytotoxicity on treated wheat seedlings. Moreover, SiO2 NPs enhanced the content of the photosynthetic pigments (chlorophylls and carotenoids), induced the accumulation of defenserelated compounds (particularly salicylic acid), and alleviated the oxidative stress via stimulation of both enzymatic (POD, SOD, APX, CAT, and PPO) and non-enzymatic (phenolics and flavonoids) antioxidant defense machinery. Collectively, our findings demonstrated the potential therapeutic role of SiO2 NPs against R. solani infection via the simultaneous activation of a multilayered defense system to suppress the pathogen, neutralize the destructive effect of ROS, lipid peroxidation, and methylglyoxal, and maintain their homeostasis within R. solani-infected plants.