Salinity is one of the major abiotic stresses that affect the plant’s growth and development. Recently, the contribution of nanoparticles (NPs) to ameliorating salinity stresses has become the new field of interest for scientists due to their special physiochemical properties in the biological system. This study is designed to examine the effects of biosynthesized silver nanoparticles (AgNPs) spherical in shape (size range between 9 and 30 nm) on morphophysiological characteristics and the antioxidant defense system of in vitro raised Maerua oblongifolia under four levels of salt stress (0, 50, 100, and 200 mM NaCl). Our findings reveal that the application of AgNPs (0, 10, 20, and 30 mg/L) to M. oblongifolia shoots significantly alleviates the adverse effects of salt stress and ameliorates plant developmental-related parameters and defense systems. High salinity elevates the oxidative damage by over-accumulation of the levels of total soluble sugars, proline, hydrogen peroxide (H2O2), and malondialdehyde (MDA). In addition, enhancing the activity of the antioxidant enzymes, total phenolic, and flavonoid content over the control. Interestingly, the application of AgNPs to salinized plants improved the growth traits and photosynthetic pigment production and caused higher enhancement in antioxidant enzyme activities. Furthermore, mitigating the oxidative damage by lowering the accumulation of proline, soluble sugars, H2O2, MDA, and total phenolic and flavonoid contents in salt-stressed plants. In general, AgNPs augmented the growth of M. oblongifolia shoots under saline conditions through different strategies; thus, AgNPs can be used as an appropriate eco-friendly approach that enhances salinity tolerance in plants.