This study investigated the effect of zinc oxide nanoparticles (ZnO-NPs) and silver nanoparticles (AgNPs) on the expression of the rsmA and rsbA genes in multi-drug resistant Proteus mirabilis. The nanoparticles were synthesized using the cell-free supernatant of P. mirabilis. Gene expression levels were quantified using quantitative Reverse Transcription Real-Time PCR (qRT-PCR) technique. The results showed that the expression of the rsmA gene was significantly downregulated in P. mirabilis isolates treated with ZnO-NPs, AgNPs, and Ag-ZnO-NPs compared to the control untreated isolate. The fold change values for gene expression were 18.32, 7.73, and 1.64 for ZnO-NPs, AgNPs, and Ag-ZnO-NPs, respectively. Similar downregulation of the rsmA gene has been observed in other bacterial species treated with silver and zinc oxide nanoparticles. Additionally, the expression of the rsbA gene was significantly downregulated in P. mirabilis treated with ZnO-NPs and AgNPs, while Ag-ZnO-NPs did not show a significant effect on rsbA gene expression. These findings suggest that ZnO-NPs and AgNPs have potential as antimicrobial agents by regulating gene expression in P. mirabilis.