The plant growth regulator 5-hydroxy-tryptamine （5-HT） has been used in agricultural production to improve crop drought resistance. The underlying molecular mechanisms of its transcriptional response are largely unknown. In this study， the simulated drought stress-related physiological and molecular mechanisms of exogenous 5-HT on Morella cerifera seedlings were elucidated， including transcriptome sequencing and the evaluation of endogenous hormone levels and antioxidant enzyme activity. The results demonstrated that abscisic acid （ABA） and jasmonic acid （JA） content in Morella cerifera fibrous roots significantly increased following 50 μmol/L 5-HT treatments but decreased in 100 μmol/L treatments. Both the malondialdehyde （MDA） content and superoxide dismutase （SOD） activity were significantly increased but hydrogen peroxide （H₂O₂） content decreased following 50 μmol/L 5-HT treatments. Based on gene set enrichment analysis （GSEA）， two-concentration levels 5-HT treatments were investigated. The differential gene set terms primarily included antioxidant activity， oxidoreductase activity， auxin and gibberellin-mediated signaling， cell wall biosynthetic， phospholipid translocation， xylan biosynthetic， pectin metabolic， secondary metabolite biosynthetic， phenylpropanoid metabolic and galacturonan metabolic process. The differentially expressed genes （DEGs） related to antioxidant enzyme activity and hormone metabolism were mainly PER， LAC， DHAR and PIN. Eight sets of co-expressed gene modules were significantly correlated with 5-HT and drought stress by the weighted gene co-expression network analysis （WGCNA）. The hub genes KAB1218346.1（LOX3）， KAB1219593.1（WRKY53）， KAB1217691.1（CZF1） were primarily associated with hormone metabolism and regulation of transcription. These key genes and their molecular regulatory mechanisms will be important targets for future research.