Nickel (Ni) stress adversely affects plant growth and biomass accumulation, posturing severe menace to crop production and food security. The current study aimed to determine the putative role of sodium nitroprusside (SNP) in mitigating Ni‐induced phytotoxicity and identify the underlying defense mechanisms in maize, which are poorly understood. Our findings showed that SNP significantly augmented plant growth, biomass, and photosynthesis‐related attributes (Fv/Fm, Fm, qP ETR, and ΦPSII) through diminishing Ni uptake and translocation in root and shoot tissues of maize under Ni stress conditions. In parallel, exogenous SNP substantially relieved maize seedlings from Ni‐induced stress by enhancing enzymatic (SOD, CAT, and GPX) and non‐enzymatic (phenol and flavonoids) antioxidant defenses and reducing oxidative stress indicators (MDA and H2O2). The results revealed that SNP treatment increased the content of organic osmolyte glycine betaine and the activity of GST, concomitantly with ATP and ionic exchange capacity (including Ca2+‐ATPase and Mg2+‐ATPase), advocating its sufficiency to promote plant growth and avert Ni‐induced stress in maize plants. The only exception was the production of organic acids (citric, oxalic, malic, and formic acids), which was reduced as SNP treatment relieved maize seedlings from Ni‐induced oxidative damage. The application of SNP also displayed higher expression of defense‐ and detoxifying‐related genes than in control treatments. Together, our data highlighted the mechanism involved in the amelioration of Ni toxicity by SNP; thus, suggesting a potential role of SNP in mitigating the adverse effects of Ni‐contaminated soils to boost growth and yield of crop plants, that is, maize.