This study seeks to investigate how the antibacterial activity of piperacillin against Pseudomonas aeruginosa can be improved by using Ephedra sinica extract, and to understand the molecular factors involved in this interaction. Given the rise of multidrug-resistant P. aeruginosa, it’s essential to develop new strategies to avoid reverting to outdated treatments from the past century. The extract of E. sinica as an agent to treat bacterial vaginosis and analyze the results obtained through MIC tests, both for E. sinica and in combination with the antibiotic piperacillin. Also, the microarray data of the gene expression profiles of P. aeruginosa treated with these agents are compared to determine the molecular mechanisms underlying the synergistic interactions. The results support the use of E.sinica extract to enhance the antibacterial effectiveness of piperacillin for treating difficult P. aeruginosa infections. The molecular investigation shows that Ephedra sinica extract boosts the antibacterial action of piperacillin against P. aeruginosa by lowering the MIC, repressing virulence gene expression, and impeding bacterial growth. In conclusion: These findings support further investigation of the combination therapy for combating P. aeruginosa infection. further study is needed to understand their efficacy against this organism fully.”