Nanoplastics, infiltrating soil ecosystems through diverse pathways such as agricultural practices, sludge application, and atmospheric deposition, present significant potential risks to global ecological systems. Through adsorption, iron oxide nanoparticles (IONPs) could reduce toxicity and bioavailability of nanoplastics in polluted soil ecosystems. However, little is known about how interactions between IONPs and polystyrene nanoplastics (PSNPs) affect plant growth. This study revealed that iron oxide nanoparticles (IONPs) effectively mitigated the uptake of polystyrene nanoplastics (PSNPs) in Perilla frutescens, demonstrating a substantial reduction of PSNPs accumulation by 46.15% in roots and 24.83% in stems. Furthermore, IONPs application significantly improved plant growth parameters, with notable increases of 20.40% in plant height and 34.22% in biomass compared to plants exposed solely to PSNPs.Compared with PSNPs alone, application of PSNPs + IONPs enhanced plant photosynthetic parameters, reduced the quantity of osmotic substances and reduced the activity of antioxidant enzymes. KEGG analysis was concentrated on photosynthetic metabolism and flavonoid synthesis. Further analysis combined with metabolic pathways revealed that IONPs treatment improved plant growth by up-regulating photosystem genes (PsbP, Psak, and PetC) and flavonoid synthesis genes (CHS, CHI, and F3H). Overall, IONPs enhance Perilla frutescens growth by upregulating photosystem-related genes and mitigate PSNPs-induced oxidative stress through flavonoid biosynthesis pathway activation. The present study provides new insights that will aid development of nano iron fertilizers capable of improving the adverse effects of nano plastics on agricultural production.