<p>Cold stress significantly impairs the rice (<i>Oryza sativa</i> L.) growth and yield, particularly in temperate regions where abrupt temperature fluctuations often occur during the early growth stages. Given the need for novel strategies to improve crop cold tolerance, we evaluated the efficacy of iron oxide nanoparticles (Fe₂O₃) in enhancing rice cold stress resilience. The reported mechanisms involve promoting plant growth and development, alleviating oxidative stress and inducing defense responses. Using RNA-seq, we analyzed the physiological and transcriptomic responses of rice to cold stress and Fe₂O₃ treatment. Under cold stress, the NPs elicited a strong antioxidant response-elevating superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, which led to a marked reduction in oxidative damage, as shown by decreased ROS and MDA levels. Transcriptomic analysis further revealed that NP treatment modulated key pathways related to carbohydrate metabolism, photosynthesis, hormone signaling, and antioxidant metabolism. Collectively, our findings establish that Fe₂O₃ nanoparticles ameliorate cold stress by preserving chloroplast structure, stomatal architecture, reduce oxidative stress marker, enhancing antioxidant defense system and stabilize photosystem and providing a promising nanozyme-based approach for rice protection against cold induce damage.</p> Graphical Abstract <p></p>