Silicon (Si) is a beneficial nutrient and is known for imparting resistance to many of the abiotic and biotic stresses in crop plants. A pot experiment was conducted in wire house to elucidate the effect of exogenous Si on growth, physiological, and biochemical activities in wheat at different phenological stages (seedling, vegetative, and maturity) under cadmium (Cd) stress. Surface sterilized seeds of Ujala-2016 wheat cultivar were sown in plastic pots. Foliar applied Si (3mM) inform of in the form of Si-NPs used in the present experiment under control (−Cd) and Cd stress (25mg/kg soil) conditions. Plants were harvested after 14 days of foliar spray at different phenological stages. The experimental treatments were arranged in completely randomized design with three replicates per treatment. Cadmium stress caused significant reduction in biomass production, photosynthetic pigments, total soluble protein (TSP), free amino acids (FAA), total soluble sugar (TSS), and phenolic contents, whereas increase of antioxidant enzymes activities such as ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), reducing sugar (RS), and proline contents as well as malondialdehyde (MDA), hydrogen peroxide (H2O2) content, and electrolyte leakage (EL) was recorded. Foliar application of Si-NPs significantly improved the growth, photosynthetic pigments, levels of flavonoids, TSP, phenolics, FAA, proline, TSS, activities of APX, CAT, POD, and SOD enzymes. The oxidative damage measured in the form of endogenous levels of H2O2 and MDA was reduced in plants treated with exogenous application of Si. Further, Si application increased mineral ions in controlled and Cd-stressed plants and significantly reduced the Cd uptake. In short, this study revealed that foliar spray of Si alleviates the adverse effect of Cd on wheat by enhancing growth, metabolite accumulation, strengthening antioxidant defense system, reducing oxidative injury, improving plant nutrient status, and decreasing the Cd uptake.