<p>Limited studies have performed the foliar application of zinc (Zn) fertilizer impact on rice consumption and the associated health risks. Here, we investigated the impact of foliar spraying with different concentrations (0.5 nm, 2 nm) and various sizes of Zn fertilizer (Zn(NO₃)₂, 30 nm Zn oxide nanoparticles (ZnO-NPs), and 300 nm ZnO-NPs) on the accumulation and subcellular distribution of Cd and Zn in rice plants. Additionally, the bioaccessibility of Cd and Zn in rice was assessed through a simulated in vitro digestion experiment to evaluate the potential risk of dietary intake of Cd. The results indicated that all treatments were able to significantly decrease the Cd concentration in grains by approximately 41% to 61% and increase the Zn concentration in grains by about 9% to 21%. This pertains to the increase in Cd fixation in the leaf cell wall. The in vitro study of simulated digestion revealed that foliar spraying of small-sized ZnO-NPs could decrease the Cd concentration and increase the Zn concentration in gastrointestinal phase, thereby reducing the bioaccessibility of Cd. However, the use of ZnO-NPs resulted in lower bioaccessibility of Zn in rice compared to the control group. The prediction, based on the daily intake of bioaccessible Cd, suggests that using large-sized and low-concentration ZnO-NPs can minimize the theoretical intake of Cd to the greatest extent possible. The application of this study is that foliar applications of ZnO-NPs can effectively enhance the nutritional quality of rice and reduce the human Cd exposure.</p>