Soil salinity degrades land worldwide, especially in semi-arid and arid regions. It arises naturally because of limited rainfall and the deposition of soluble salts at the soil surface, exacerbated by human activities such as more flood irrigation, excessive use of fertilizers, and inadequate drainage. The current study was conducted to assess the synergistic effect of melatonin (ML) and strigolactone (SL) on maize seedlings to ameliorate the harmful effects of salinity. The 250 mu M ML and 25 mu M SL were applied alone or in combination on maize seedlings grown under salinity stress (100 mM NaCl) and normal conditions (control, Ck). Salinity stress reduced growth and physiological parameters, but ML and SL, especially in combination, significantly improved these traits. Salinity stress significantly (p < 0.05) augmented H2O2, malonaldehyde (MDA) contents, electrolyte leakage, and Na+ concentration in maize seedlings as compared to Ck. Nevertheless, the combined application of ML and SL alleviated the oxidative stress caused by salinity stress by increasing the activities of enzymatic antioxidants (superoxide dismutase, peroxidase, ascorbate peroxidase, and catalase) and decreasing the levels of H2O2, MDA, electrolytes leakage, and Na+ concentration. In addition, free proline, soluble protein, total soluble sugar, total phenolics, and K+ contents were remarkably stimulated by applying ML + SL under saline conditions. This study demonstrates that ML and SL synergistically enhance maize resilience to salinity stress by strengthening antioxidant defenses, improving osmotic balance, and maintaining ion homeostasis. These findings suggest that exogenous ML and SL application is a promising strategy for cultivating maize in salt-affected areas.