The present study demonstrated the possible impacts of iron oxide nanoparticles (Fe NPs) on the alleviation of toxic effects of cadmium (Cd) in wheat and enhance its growth, yield, and Fe biofortification. A pot experiment was conducted in historically Cd-contaminated soil using five levels of Fe NPs (0, 5, 10, 15, and 20 ppm) by soil and foliar application methods. The plants were harvested after 125 days of growth while vegetative parameters, antioxidant capacity, electrolyte leakage (EL) in leaves as well as Cd, and Fe concentrations in wheat grains, roots, and shoots were measured. The results showed that the application of Fe NPs mitigated the Cd toxicity on wheat growth and yield parameters. The exogenous application of Fe NPs enhanced the wheat morphological parameters, photosynthetic pigments, and dry biomass of shoots, roots, spike husks and grains. The activities of super oxide dismutase and peroxidase increased, whereas EL reduced from wheat leaves over control. The Cd concentrations were reduced in wheat tissues and grains whereas Fe concentrations increased with Fe NPs application in a dose-additive manner. The current work suggested that the application of Fe NPs on wheat in Cd-contaminated soils could be employed to improve growth, yield and Fe biofortification as well as reduction in Cd concentrations in plants.