Selenium (Se) plays an important role in the growth of plants. Alfalfa (Medicago sativaL.) is a perennial legume forage crop with high nutritional value and Se-rich functions. Many studies have shown that selenium can promote alfalfa growth, but few have explored the molecular biology mechanisms behind this effect. In this study, alfalfa was divided into two groups. One group was sprayed with sodium selenite (Na2SeO3) and the other group was sprayed with distilled water as a control. This study determined the growth, reproductive traits, physiological changes, transcriptome and metabolome of both groups of alfalfa. We found that foliar spraying of 100 mg/L Na2SeO3could significantly increase the growth rate, dry weight, total Se content, amount of pollen per flower, pollen viability, pod spirals, and seed number per pod of alfalfa plants. The level of chlorophyll, soluble protein, proline, and glutathione also increased dramatically in Na2SeO3-sprayed alfalfa seedlings. After transcriptome and metabolome analysis, a total of 614 differentially expressed genes (DEGs) and 1500 differentially expressed metabolites (DEMs), including 26 secondary differentially metabolites were identified. The DEGs were mainly enriched in MAPK signaling pathway, phenylpropanoid biosynthesis, isoflavonoid biosynthesis, cutin, suberine, and wax biosynthesis, and glycerolipid metabolism. The DEMs were mainly enriched in flavone and flavonol biosynthesis, carbon metabolism, glyoxylate and dicarboxylate metabolism, nitrogen metabolism, and phenylpropanoid biosynthesis. Integrative analysis of transcriptome and metabolome showed that the foliar spraying of Na2SeO3mainly affects phenylpropanoid biosynthesis to promote alfalfa growth.