The reduction of cadmium (Cd) accumulation in rice grains through biofortification of essential nutrients like zinc (Zn) and silicon (Si) is an area of study that has gained significant attention. However, there is limited understanding of the mechanism of Zn/Si interaction on Cd accumulation and remobilization in rice plants. This work used a pot experiment to examine the effects of Zn and Si applied singly or in combination on the physiological metabolism of Cd in different rice organs under Cd stress. The results revealed that: Zn/Si application led to a significant decrease in root Cd concentration and reduce the value of Tf Soil-Root in filling stage. The content of phytochelatin (PCs, particularly PC2) and glutathione (GSH) in roots, top and basal nodes were increased with Zn/Si treatment application. Furthermore, Zn/Si treatment promoted the distribution of Cd in cell wall during Cd stress. These findings suggest that Zn/Si application facilitates the compartmentalization of Cd within subcellular structures and enhances PCs production in vegetative organs, thereby reducing Cd remobilization. Zn/Si treatment upregulated the metabolism of amino acid components involved in osmotic regulation, secondary metabolite synthesis, and plant chelating peptide synthesis in vegetative organs. Additionally, it significantly decreased the accumulation of Cd in globulin, albumin, and glutelin, resulting in an average reduction of 50.87% in Cd concentration in milled rice. These results indicate that Zn/Si nutrition plays a crucial role in mitigating heavy metal stress and improving the nutritional quality of rice by regulating protein composition and coordinating amino acid metabolism balance.