Cadmium (Cd) pollution leads to reduced crop yields and poses a threat to human health, making it an important environmental and agricultural safety issue. Selenium [Se(V)] has been shown to alleviate Cd stress in plants; however, the mechanisms underlying Se-mediated protection against Cd toxicity remain largely unclear. In this study, we investigated the physiological and molecular mechanisms of Se(W)-alleviated Cd toxicity in strawberry plants through physio-biochemical and transcriptomic analyses. Our results showed that foliar spraying with Se (IV) increased photosynthetic efficiency, reduced Cd-induced oxidative damage by enhancing antioxidant enzyme activities and soluble sugar contents, thereby improving Cd stress tolerance. Transcriptomic profiling revealed 477 common differentially accumulated transcripts (DATs), predominantly enriched in transporter activity, oxidoreductase function, and antioxidant-related processes. Notably, seven key genes involved in Cd efflux, chelation, secondary metabolite transport and nutrient uptake (FvPCR9-like, FvCBP-like, FvWATI-like, FvMOT1, FvY1476gO214O, FvNR12.1 and FvZIP8) exhibited opposite expression patterns under Se(W) and Cd treatments. Supplementation with Se(IV) also modulated phytohormone signaling, nitrogen metabolism and carbon metabolism pathways, providing a multi-dimensional approach to mitigating Cd-induced physiological disruptions. This study provides novel insights into Se(IV)-mediated Cd stress adaptation, and offers promising strategies for developing low-Cd-accumulating crops, addressing critical environmental and agricultural challenges associated with heavy metal contamination.