Abstract: Rice plays an important role in ensuring food security and controlling heavy metal pollution in China, while cadmium (Cd) accumulation in rice grains not only threatens food safety but also poses risks to human health. A field plot experiment was conducted to systematically evaluate the effects of foliar application of different concentrations of Zn/Se compounds during the grain-filling stage on Cd accumulation in rice, as well as on the Zn and Se content and bioaccessibility of Cd, Zn, and Se in rice grains. The aim was to identify the optimal ZnSe combination for simultaneously reducing grain Cd and increasing Zn and Se levels, and to further investigate its effects on root surface iron plaque formation and Cd sequestration, Cd transport within the rice plant, and the subcellular distribution and chemical forms of Cd in the first node, in order to elucidate the mechanisms of ZnSe in regulating Cd uptake and translocation. The results showed that foliar application of 2 g/L Zn combined with 4 mg/L Se significantly reduced Cd content in grains by 26.1% and increased grain Zn and Se content by 49.2% and 157.1%, respectively. This treatment also decreased Cd bioaccessibility in grains by 18.2%, while enhancing Zn and Se bioaccessibility by 80.1% and 282.4%, respectively, making it the optimal combination for simultaneously reducing Cd and enriching Zn and Se in rice grains. The ZnSe treatment reduced Cd content in the iron plaque on the root surface by 20.6% and in grains by 27.3%, whereas Cd content in other stem and leaf tissues and in the first internode increased significantly by 41.9% and 29.3%, respectively. Furthermore, the ZnSe treatment enhanced Cd transport from the iron plaque to the roots but inhibited its transport from the roots to the first node and from the first node and flag leaves to the grains. At the subcellular level, ZnSe application significantly increased the proportion of Cd in the cell walls of the first node by 19.2% and decreased its proportion in organelles by 24.4%. These findings indicate that foliar application of ZnSe reduces Cd accumulation in rice grains primarily by decreasing Cd in root surface iron plaques and enhancing its fixation in the cell walls of the first node.