Key message <p>Polyploid rice exhibits superior cadmium tolerance via enhanced antioxidant activity, reduced Cd accumulation, and transporter regulation, with zinc nanoparticles further mitigating toxicity and modulating stress-responsive genes.</p> Abstract <p>Cadmium (Cd) contamination poses a serious threat to rice production by impairing plant growth and yield. To investigate the mechanisms of Cd tolerance, we compared diploid rice (E22) and its polyploid counterpart (T42) under Cd stress (50 mg&#xa0;kg⁻¹ soil) with or without zinc supplementation (25 mg&#xa0;kg⁻¹ soil). Upon Cd exposure, E22 exhibited a 7.8% decline in plant weight and seed set, while T42 experienced only a 4.71% reduction in plant weight, demonstrating its enhanced tolerance to Cd toxicity. Consistently, Cd accumulation was markedly lower in T42 across multiple tissues. Under Cd stress, T42 maintained lower levels of H₂O₂ and malondialdehyde while exhibiting enhanced antioxidant activity, including elevated peroxidase, superoxide dismutase, catalase, and glutathione, compared to E22. The more complete organelles in T42 likely contributed to its improved Cd tolerance. Notably, supplementation with ZnO-NPs reduced Cd accumulation in both diploid and polyploid rice. Transcriptomic analysis revealed that starch metabolism-related genes (<i>OsISA1</i> and <i>OsISA2</i>) were strongly expressed in T42, whereas tubulin genes (<i>OsTB16</i> and <i>OsTB50</i>) were strongly expressed in T42 under Zn treatment. In contrast, photosynthesis-related genes show remarkable differential expressions between E22 and T42, suggesting different adaptive strategies in E22 and T44, as evidenced by impaired photosynthesis in E22 under stress. Overall, these findings demonstrate that polyploid rice possesses enhanced resilience to Cd stress through coordinated regulation of tubulin, metal transporters, and antioxidant systems, with ZnO-NPs further mitigating Cd toxicity.</p>