Cadmium stress is a major threat to plant growth and survival worldwide. The current study aims to green synthesis, characterization, and application of zinc-oxide nanoparticles to alleviate cadmium stress in maize (Zea mays L.) plants. In this experiment, two cadmium levels (0, 0.6 mM) were applied to check the impact on plant growth attributes, chlorophyll contents, and concentration of various primary metabolites and antioxidants under exogenous treatment of zinc-oxide nanoparticles (25 and 50 mg L-1) in maize seedlings. Tissue sampling was made 21 days after the zinc-oxide nanoparticles application. Our results showed that applying cadmium significantly reduced total chlorophyll and carotenoid contents by 52.87% and 23.31% compared to non-stress. In comparison, it was increased by 53.23%, 68.49% and 9.73%, 37.53% with zinc-oxide nanoparticles 25, 50 mg L-1 application compared with cadmium stress conditions, respectively. At the same time, proline, superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase contents were enhanced in plants treated with cadmium compared to non-treated plants with no foliar application, while it was increased by 12.99 and 23.09%, 23.52 and 35.12%, 27.53 and 36.43%, 14.19 and 24.46%, 14.64 and 37.68% by applying 25 and 50 mg L-1 of zinc-oxide nanoparticles dosages, respectively. In addition, cadmium toxicity also enhanced stress indicators such as malondialdehyde, hydrogen peroxide, and non-enzymatic antioxidants in plant leaves. Overall, the exogenous application of zinc-oxide nanoparticles (25 and 50 mg L-1) significantly alleviated cadmium toxicity in maize. It provides the first evidence that zinc-oxide nanoparticles 25 ~ 50 mg L-1 can be a candidate agricultural strategy for mitigating cadmium stress in cadmium-polluted soils for safe agriculture practice.