Microplastics (MPs) can act as carriers for environmental pollutants; therefore, MPs combined with heavy metal pollution are attracting increasing attention from researchers. In this study, the potential of the plant growth-promoting bacterium Bacillus sp. SL-413 to mitigate the stress caused by exposure to both MPs and cadmium (Cd) in sorghum plants was investigated. The effects of inoculation on sorghum biomass were investigated using hydroponic experiments, and evaluation of Cd accumulation and enzyme activity changes and transcriptomics approaches were used to analyze its effect on sorghum gene expression. The results showed that combined polyethylene (PE) and Cd pollution reduced the length and the fresh and dry weights of sorghum plants and thus exerted a synergistic toxic effect. However, inoculation with the strains alleviated the stress caused by the combined pollution and significantly increased the biomass. Inoculation increased the dry weights of the aboveground and belowground parts by 11.5-44.6% and 14.9-38.4%, respectively. Plant physiological measurements indicated that inoculation reduced the reactive oxygen species (ROS) content of sorghum by 10.5-27.2% and thereby alleviated oxidative stress. Transcriptome sequencing showed that exposure to combined Cd+MP contamination induced downregulation of gene expression, particularly that of genes related to amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, and plant hormone signal transduction, in sorghum. However, inoculation with Bacillus sp. SL-413 resulted in an increase in the proportion of upregulated genes involved in signal transduction, antioxidant defense, cell wall biology, and other metabolic pathways, which included the phenylpropanoid biosynthesis, photosynthesis, flavonoid biosynthesis, and MAPK signaling pathways. The upregulation of these genes promoted the tolerance of sorghum under combined Cd+MP pollution stress and alleviated the stress induced by these conditions. This study provides the first demonstration that plant growth-promoting bacteria can alleviate the stress caused by combined pollution with MPs and Cd by regulating plant gene expression. These findings provide a reference for the combined plant-microbial remediation of MPs and Cd.