Inducing resistance by prior application of nanochitosan, chitosan, and vitamins B3 (nicotinic acid), B9 (folic acid) and C (ascorbic acid), to counteract wheat leaf rust caused by Puccinia triticina Eriks. was investigated in two field trials during 2021-2022 and 2022-2023 growing seasons. The tested materials were sprayed pre-infection with the disease on a susceptible wheat cultivar (Gemmiza-7). The response of the treated plants changed to moderately resistant (MR) by nanochitosan and folic acid (Vit. B9), while they changed to moderately susceptible (MS) by nicotinic acid (Vit. B3) and ascorbic acid (Vit. C) as compared to the susceptible response in the fungicide (propiconazole 25%) and untreated control. All treatments offered good levels of disease protection, which reached 95.0% in the case of nanochitosan and folic acid comparable to the fungicide (propiconazole 25%), being 93.75%. Also, they significantly reduced the average coefficient of infection (ACI). The best treatments were nanochitosan and folic acid, since they reduced ACI to 4 comparable to the fungicide (propiconazole 25%), being 5 and untreated control, being 80. In addition, these treatments resulted in the highest increase in grain yield components. Metabolic aspects analyses revealed a significant increase in peroxidase (POX) and catalase (CAT) antioxidant enzyme activity as well as total chlorophyll and total phenols due to the tested treatments. The use of chitosan nanoparticles and vitamins B3, B9 and C may be an environmentally friendly strategy to induce resistance against leaf rust of wheat.