Nitric oxide (NO) plays a significant role in plant drought resistance. However, the effects of the exogenous application of NO to crops under drought stress vary within and among species. In this study, we explored the influence of exogenous sodium nitroprusside (SNP) on the drought resistance of soybean leaves in the full flowering stage using two varieties: drought-tolerant HN44 and non-drought-tolerant HN65. Spraying SNP on soybean leaves at the full flowering period under drought stress improved the NO content in soybean leaves. The activities of nitrite reductase (NiR) and nitrate reductase (NR) in leaves were affected by NO inhibition. The activity of antioxidant enzymes in leaves increased with the extension of SNP application time. Contents of osmomodulatory substances, including proline (Pro), soluble sugar (SS), and soluble protein (SP) increased gradually with the extension of SNP application time. The malondialdehyde (MDA) content decreased as the NO content increased, thus reducing membrane system damage. Overall, spraying SNP reduced damage and improved the ability of soybean to cope with drought. This study explored the physiological changes of SNP soybean under drought stress and provided theoretical basis for improving drought-resistant cultivation of soybean.