Background <p><i>Pseudomonas aeruginosa</i> is a multidrug-resistant (MDR) pathogen, and efflux pumps such as MexCD-OprJ and MexEF-OprN play a key role in its antibiotic resistance. This study evaluated the putative effects of curcumin and methanolic extracts of <i>F. excelsior</i> L. and <i>G. glabra</i> L. on the expression of these efflux pumps, as well as their role in mediating antibiotic resistance.</p> Methods and results <p>In this study, MDR <i>P. aeruginosa</i> clinical strains were used to determine the minimum inhibitory concentrations (MICs) of tobramycin and ciprofloxacin in the presence and absence of curcumin and selected plant extracts (<i>F. excelsior</i> L. and <i>G. glabra</i> L.) and curcumin. Real-time PCR was used to assess changes in efflux pump gene expression in tested strains. A significant positive correlation was identified between resistance to the tested antibiotics and increased expression of MexCD-OprJ and MexEF-OprN, as determined by Spearman’s rank correlation using SPSS (<i>p</i> &lt; 0.05). Treatment with the extracts, individually and in combination, resulted in a reduction in the expression levels of both efflux genes (<i>p</i> &lt; 0.05), with the combined treatment showing the greatest effect. These findings were supported by colony count and turbidity assays, as evidenced by &gt; 80% reduction in viable counts and decreased turbidity in treated groups.</p> Conclusion <p>Overexpression of MexCD-OprJ and MexEF-OprN is a key factor contributing to MDR in <i>P. aeruginosa</i>. Treatment with curcumin, <i>F. excelsior</i> L. and <i>G. glabra</i> L. extracts—especially in combination, suggesting potential for suppression of efflux gene expression and enhanced antibiotic efficacy.</p>