Cadmium (Cd) in the food system poses a serious threat to human health. The evidence on strigolactones-mediated alleviation of abiotic stress signaling and eliciting physiological modifications in plants is scarce. Therefore, this experiment was conducted to explore the role of exogenous applied strigolactone (SL) in alleviating the toxic effects of Cd and to unravel its physiological, biochemical, and molecular mechanisms in wheat. Excessive accumulation of Cd drastically reduces growth attributes (−15%), nitric oxide signaling, and photosynthetic pigments by increasing oxidative stress biomarkers. Foliar applied SL (4 μM) decreased the Cd-induced growth inhibition (+10%), lessened plant Cd contents (−38% and −36%), shielded chlorophyll pigments (+25%), and considerably decreased Cd-induced oxidative stress in wheat. Moreover, SL applied on wheat foliage remarkably enhanced shoot and root nitric oxide content (+122% and +156%) and nitric oxide synthase activity (104% and 92%) in wheat, efficiently mitigating the Cd-induced suppression of superoxide dismutase and peroxidase, elevating the expression of genes encoding antioxidant defense system. The results of the current research exhibit that SL (GR24) could be a potential candidate for detoxification of Cd by reducing Cd contents, elevating the expression of genes encoding antioxidant defense system, and protecting wheat plants from oxidative stress by indirectly reducing oxidative stress biomarkers andsubsequently contributing to decreasing the possible risk of Cd contamination.