The razor clam (Sinonovacula constricta) is a key species in marine aquaculture, known for its wide salinity adaptation, and potential for cultivation in saline-alkaline water. Understanding its response mechanisms is crucial for expanding its farming into these regions. This study reveals the response mechanisms of S. constricta in response to low-salinity alkaline stress through a combined analysis of transcriptomics and metabolomics. After 24 h of salt-alkali stress (SA group), 1378 differentially expressed genes (DEGs) were identified, with enriched pathways including glycerophospholipid metabolism, serine, taurine, and hypotaurine metabolism. Additionally, 341 significantly different metabolites (SDMs) were found, primarily involved in taurine and hypotaurine metabolism, purine metabolism, and the FoxO signaling pathway, etc. Both DEGs and SDMs were notably enriched in hypotaurine metabolism, glycerophospholipid metabolism, and the mTOR signaling pathway, showing significant upregulation in the SA group. Correlation analysis found that the integrated regulatory network was involved in the synthesis of taurine, glycerophospholipids, and L-glutamic acid, and the metabolism of 3-mercaptopropionic acid. These results suggest that low salinity and alkalinity induce stress responses in S. constricta by regulating osmotic balance, phospholipid synthesis, and lipid metabolism. This study offers insights into the molecular mechanisms of salt-alkali response in S. constricta.