Under natural conditions, various abiotic and biotic constrains act on the plants. Root-knot nematodes, particularly Meloidogyne incognita serve as one of the chief biotic constrains in the agriculture sector, ultimately leading to immense economic losses globally. Nowadays, plant signaling molecules such as gasotransmitters and phytohormones have gained importance for stress-curtailing roles. Therefore, the current study was designed to decode the role of nitric oxide (NO) in growth promotion and stress diminution in Solanum lycopersicum under M. incognita stress. Surface sterilized tomato seeds were pre-treated for 4 h with different concentrations (50, 100 and 200 mu M) of sodium nitroprusside (SNP, NO donor). The treated seeds were allowed to germinate in autoclaved petri plates lined with filter paper. After germination, the seedlings were inoculated with 5 s-stage juveniles per seedling. The experiment was terminated after 10 days of nematode inoculation and different parameters were assessed. Results revealed that inoculation of nematodes reduced the growth in terms of length and weight and level of photosynthetic pigments of S. lycopersicum seedlings and increased the content of stress markers such as hydrogen peroxide (H2O2) and malondialdehyde (MDA) leading to oxidative stress in the seedlings. Additionally, the activity of enzymatic and non-enzymatic antioxidants and the content of proline and phenolic compounds were found to be enhanced in nematode-inoculated seedlings. Glutathione tagging was also assessed using a confocal microscope, indicating an enhanced glutathione level in nematode-inoculated seedlings. Seed priming with SNP mitigated the negative effect of nematode stress by alleviating the level of stress markers (H2O2 and MDA) and further elevating the activity of antioxidants and phenolic compounds. Seed priming with SNP also resulted in a significant decrease in number of galls formation and increased the growth of S. lycopersicum seedlings. These findings indicate a crucial role of NO in elemental defense response during nematode stress in plants.