Strategies to reduce the risk of drought damage are urgently needed as intensified climate change threatens agricultural production. One potential strategy was using nanomaterials (NMs) to enhance plant resistance by regulating various physiological and biochemical processes. In the present study, 10 mg kg−1manganese ferrite (MnFe2O4) NMs had the optimal enhancement to elevate the levels of biomass, photosynthesis, nutrient elements, and polysaccharide in rice by 10.9–525.0%, respectively, under drought stress. The MnFe2O4NMs were internalized by rice plants, which provided the possibility for rice to better cope with drought. Furthermore, as compared with drought control and equivalent ion control, the introduction of MnFe2O4NMs into the roots significantly upregulated the drought-sensing geneCLE25(29.4%) and the receptor geneNCED3(59.9%). This activation stimulated downstream abscisic acid, proline, malondialdehyde, and wax biosynthesis by 23.3%, 38.9%, 7.2%, and 26.2%, respectively. In addition, 10 mg·kg−1MnFe2O4NMs significantly upregulated the relative expressions ofOR1,AUX2,AUX3,PIN1a, andPIN2, and increased IAA content significantly, resulting in an enlarged root angle and a deeper and denser root to help the plant withstand drought stresses. The nutritional quality of rice grains was also improved. Our study provides crucial insight for developing nano-enabled strategies to improve crop productivity and resilience to climate change.