Whole-genome doubling or polyploidy increases plants' tolerance to biotic and abiotic stress. Cadmium (Cd) damages the plant's metabolic system, leading to decreased plant development. The role of tetraploidy and iron nanoparticles (Fe NPs) in minimizing Cd toxicity in rice was investigated in this work. Diploid (E285) and tetraploid (T485) rice lines were treated with Cd (100 μM) and different doses of Fe NPs (0, 10, 25, and 50 mg L⁻¹). The Cd exposure substantially decreased agronomic traits (root and shoot length, shoot and root fresh weight), chlorophyll contents, and antioxidant enzyme activity and increased reactive oxygen species (ROS). The Cd toxicity effect was more pronounced in diploid rice than in tetraploid rice. The application of Fe NPs to Cd-contaminated rice plants reversed the detrimental consequences of Cd in tetraploid and diploid rice cultivars, verified by the substantial upturn in plant growth parameters, chlorophyll contents, decreased ROS, and increased levels of antioxidant enzymes. The Cd uptake was significantly reduced by tetraploidy and Fe NPs, which negatively controlled the expression patterns of Cd transporter genes (like OsNRAMP2 and OsHMA2). The strongest association was seen between diploid rice and cadmium levels in seedlings. Transmission electron microscopy revealed that Cd, especially in diploid rice, caused cell structure damage that Fe NPs and tetraploidy almost repaired. This study demonstrated that tetraploidy and Fe NPs could alleviate Cd toxicity by lowering Cd accumulation, ROS, and cell damage.