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Cadmium (Cd) is highly toxic to wheat, hindering growth due to oxidative damage. Salicylic acid (SA) acts as a stress signal, increasing the nutrient acquisition by reducing the uptake of Cd.In this study, we investigated the impact of foliar application of 0.5 mM SA on two wheat varieties, V1 = Akbar-19 and V2 = Anaj-17, subjected to three times with 500 μM CdCl2stress in half-strength Hoagland solution. Cd stress negatively impacted wheat growth, chlorophyll. Shoot length reduced by 8.09% (Akbar-19) and 5.92% (Anaj-17). Root length dropped by 14.5% (Akbar-19) and 11.3% (Anaj-17). Chlorophyll content lowered by 17.9% (Akbar-19) and 11.1% (Anaj-17). Carotenoids decreased by 42.2% (Akbar-19) and 23.2% (Anaj-17). Cd stress led to reduced nutrient uptake (sodium, potassium, calcium, phosphorous) in roots, stems, leaves. However, SA applications effectively mitigated the harmful impacts of Cd stress in wheat varieties. SA increased photosynthetic pigments, enzymatic and non-enzymatic antioxidants, and osmoprotectants, while maintaining nutrient content in the plants. Furthermore, SA enhanced the activity of key antioxidant enzymes such as peroxidase dismutase, superoxide dismutase, and catalase by 9.84 and 13.7%, 11.2 and 14.3%, and 40.2 and 45.8% in Akbar-19 and Anaj-17 of wheat varieties exposed to Cd stress as compared to control-no SA. Plant defense upregulation improved nutrient uptake in roots, stems, leaves under SA. Anaj-17 outperformed Akbar-19 in growth, photosynthesis, antioxidants, nutrient uptake under Cd stress. In crux, Cd toxicity was reduced by SA in wheat by modulating the plant antioxidant defense and osmolyte production.