Pseudomonas aeruginosa, a significant drug-resistant pathogen, is a major issue in hospitals, especially the wide range infection in intensive care units, due to its complicated antibiotic resistance mechanisms and protective biofilms formation. The study aimed at evaluation the potential antibacterial activity of Sidr, Talh, and Sommra honey obtained from Al-Bahha region, Saudi Arabia against 17 drug-resistant P. aeruginosa strains collected from patients of various ages at King Abdulaziz University Hospital. The identification and antimicrobial susceptibility testing were performed throughout disk diffusion and Vitek 2 automate system, and genetic manipulation. Our results showed that Talh, Sidr and Sommra honey was exhibited high antimicrobial efficiency against bacterial infection, also indicated the synergistic efficiency of honey supplementation in fighting a drug-resistant P. aeruginosa strains with synthetic antibiotics. This study outcomes pointed out the crucial role of natural honey supplementation in healthcare and bacterial infections control, which in turn is consistent with the Saudi Arabia's goals for improving public health and combating infectious diseases. These results need a further exploration into honey's potential as a natural approach to managing infections resistant to antibiotics and highlight its significance in developing novel healthcare solutions that align with the Kingdom of Saudi Arabia's objectives for advancing medical science.