Soil salinization is a major factor that reduces crop yields. There are some plant growth-promoting rhizobacteria (PGPR) that can stimulate and enhance the salt tolerance of plants near their roots in saline–alkali environments. Currently, there is relatively little research on PGPR in rice saline–alkali tolerance. In the early stages of this study, a strain of Microbacterium ginsengiterrae S4 was screened that could enhance the growth of rice in a laboratory-simulated saline–alkali environment (100 mM NaCl, pH 8.5). The experiment investigated the effects of S4 bacteria on the growth, antioxidant capacity, and osmotic regulation of rice seedlings under saline–alkali stress. RNA-Seq technology was used for transcriptome sequencing and UPLC-MS/MS for metabolite detection. Research has shown that S4 bacteria affect the growth of rice seedlings under saline–alkali stress through the following aspects. First, S4 bacteria increase the antioxidant enzyme activity (SOD, POD, and CAT) of rice seedlings under saline–alkali stress, reduce the content of MDA, and balance the content of osmotic regulatory substances (soluble sugar, soluble protein, and proline). Second, under saline–alkali stress, treatment with S4 bacteria caused changes in differentially expressed genes (DEGs) (7 upregulated, 15 downregulated) and differentially metabolized metabolites (101 upregulated; 26 downregulated) in rice seedlings. The DEGs are mainly involved in UDP-glucose transmembrane transporter activity, while the differentially metabolized metabolites are mainly involved in the ABC transporters pathway. Finally, key genes and metabolites were identified through correlation analysis of transcriptomes and metabolomes, among which OsSTAR2 negatively regulates L-histidine, leading to an increase in L-histidine content. Furthermore, through gene correlation and metabolite correlation analysis, it was found that OsWRKY76 regulates the expression of OsSTAR2 and that L-histidine also causes an increase in 2-methyl-4-pentenoic acid content. Based on the above analysis, the addition of S4 bacteria can significantly improve the tolerance of rice in saline–alkali environments, which has a great application value for planting rice in these environments.