Salinity in the soil is one of the limiting factors affecting agricultural productivity and plant health, threatening food security. Selenium (Se), a beneficial trace element, is attractive because of its remarkable potential for regulating abiotic stresses in plants. This study aimed to understand how Arabidopsis thaliana responds to salinity environment and the underlying molecular mechanisms of gene regulation and metabolites accumulation in Se-induced salinity tolerance. Our results showed that Se was affective in enhancing plant’s ability to alleviate salt-induced oxidative stress to significant levels in sos1 plants compared to wild type plants. Se addition enhanced Arabidopsis thaliana salt tolerance by upregulating antioxidant systems, led to a significant increase in the aboveground fresh weight (33.79%), SOD (12.90%), POD (45.81%), GSH (45.59%) and soluble protein (10.77%). Transcriptome analysis identified the phytohormone signaling, glycerophospholipid metabolism, starch and sucrose metabolism, arginine and proline metabolism, and phenylpropanoid biosynthesis in Se-treated salt stressed sos1 plants under salt stress, mainly involving the genes AUX1, IAA, PYL, and scrk. The metabolomic analysis identified 668 differentially expressed metabolites, including those involved in arginine and proline metabolism as well as lipid metabolism, which were accumulated in Se-treated plants under salt stress. Integrative multi-omics analysis revealed significant enrichment at the gene and metabolite level in starch and sucrose metabolism, and phenylpropanoid biosynthesis. The current findings provided critical mechanisms for Se-mediated alleviation of salt stress from physiological, transcriptional and metabolic aspects in plants.