Cultivating crops often presents numerous challenges, including resource loss such as water, fertilizers, and pesticides, as well as the spread and escalation of infections. Nanotechnology offers promising solutions to enhance plant immunity and resolve agricultural issues. In this study, in order to prevent Fusarium-wilt disease in eggplants, we concentrated on the simple manufacture of colloidal ferric oxide nanoparticles (Fe2O3 NPs) as a promising nanofertilizers. To evaluate the effectiveness of systemic resistance (SR) development, we evaluated markers of metabolic resistance, photosynthetic pigments, plant protection, and disease index (DI). Positively, Fe2O3 NPs exhibit significant antifungal activity against Fusarium oxysporum. However, when applied at a concentration of 20 µg/mL, Fe2O3 NPs proved to be the most effective treatment, reducing the percent disease index (PDI) from 82.5% in infected control plants to 22.5%. Similar results were observed with a concentration of 10 µg/mL Fe2O3 NPs. In both healthy and diseaseed plants, Fe2O3 NP treatments also showed beneficial effects on the activity of antioxidant enzymes, osmolytes, and photosynthetic pigments. Notably, compared to untreated Fusarium-infected plants, the application of Fe2O3 NPs at a concentration of 20 µg/mL significantly increased the levels of osmolyte, comprising soluble sugar, proline, and soluble protein, by 32.88%, 47.09%, and 31.34%, respectively. Furthermore, in both healthy and diseased eggplants, Fe2O3 NPs at a concentration of 20 µg/mL increased the levels of photosynthetic pigments, osmolytes, peroxidase, polyphenol oxidase, catalase, and superoxide dismutase enzymes. Overall, our research findings indicates that Fe2O3 NPs can successfully decreased the harmful effects that F. oxysporum causes to infected eggplants. With their promising therapeutic potential, these nanoparticles provide a secure and effective substitute for chemical fungicides in the management of Fusarium wilt disease.