Abstract <p>Melatonin (MT), a small indoleamine molecule, regulates abiotic stress resistance. This study investigated the effects of exogenous MT on the growth, physiology, and secondary metabolites of <i>Eleutherococcus senticosus</i> seedlings under NaCl stress (100 and 200 mmol/L by foliar application of MT at different concentrations (50, 100, 200, and 300 μmol/L). Salt stress significantly impaired osmotic regulation, antioxidant capacity, and secondary metabolite accumulation in <i>E. senticosus</i> seedlings. Exogenous MT significantly alleviated these negative impacts.MT application notably improved photosynthetic parameters and fluorescence parameters. It enhanced stress tolerance by boosting osmolyte levels (proline, soluble sugars, and soluble proteins) and antioxidant enzyme activities (SOD, CAT, POD, APX), thereby suppressing reactive oxygen species and reducing membrane damage. MT also application significantly reduced the uptake of Na⁺ in leaves under salt stress, which lowered the Na⁺/K⁺, Na⁺/Ca²⁺, and Na⁺/Mg²⁺ ratios, it also mitigated the salt-induced imbalance in ion homeostasis. Furthermore, exogenous MT elevated the levels of secondary metabolites (spikenoside, eleutheroside E, hyperoside, chlorogenic acid, isofraxidin) in salt-stressed seedlings. In conclusion, foliar application of MT suppressed reactive oxygen species generation, enhanced antioxidant capacity and osmotic adjustment, reduced membrane lipid peroxidation, improved photosynthetic efficiency, and increased secondary metabolite accumulation, ultimately enhancing salt tolerance in <i>E.&#xa0;senticosus</i> seedlings. Among the concentrations tested, 200 μmol/L MT showed the most significant alleviating effect on NaCl stress. This study provides theoretical insights into MT-mediated salt stress mitigation mechanisms in <i>E. senticosus</i>.</p>