Abstract: Suaeda australis, a key halophytic species in southern China’s coastal ecosystems, plays a vital role in stabilizing fragile ecosystems due to its remarkable salt tolerance. Addressing escalating coastal soil salinization, this study systematically investigated the molecular mechanisms underlying its salt adaptation through integrated physiological, transcriptomic, and functional validation approaches. Under different salt concentration treatments (ST1 and ST2), S. australis exhibited significantly enhanced activities of antioxidant enzymes (CAT, SOD, POD) alongside elevated malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) levels, indicating activation of antioxidant defenses to mitigate oxidative damage under high-salinity stress. Transcriptome profiling identified 2434 differentially expressed genes (1568 upregulated and 866 downregulated). Gene Ontology (GO) and KEGG enrichment analyses revealed these genes to be predominantly associated with antioxidant responses, osmotic regulation, signal transduction, and carbon metabolism. Additionally, a total of 146 transcription factors related to salt stress response were identified. The RTq-PCR validation results were consistent with transcriptome data, further confirming the critical role of these genes in the salt stress response. Notably, the MYB family gene Sau00119 was significantly upregulated in ST2, highlighting its crucial role in the salt tolerance mechanism of S. australis. These findings provide new insights into the salt tolerance mechanism of S. australis and offers potential gene targets for the genetic improvement of salt tolerant plants.