Background & Objective: Efflux pump inhibitors (EPIs) can block efflux pumps and are helpful in potentiating the activity of aminoglycosides against Pseudomonas aeruginosa. The present study compared the effects of phenylalanine-arginine beta naphthylamide (PAβN) and curcumin on aminoglycoside minimum inhibitory concentration (MIC) on Pseudomonas aeruginosa clinical isolates. Materials & Methods: For this descriptive-analytical study, 100 clinical isolates of Pseudomonas aeruginosa were collected and identified by differential diagnostic tests. The MICs of amikacin, gentamicin, and tobramycin were evaluated before and after adding EPIs using a micro-broth dilution test. Results: The bacteria were isolated from different types of samples, including urine (26 isolates), sputum (37 isolates), ulcers (20 isolates), catheters (eight isolates), blood (five isolates), feces (two isolates), and eyes (two isolates). Overall, 60% of the isolates were obtained from males (mean age = 47.85), and 40% from females (mean age = 44.76). In the MIC test, 11 (25.5%), 15 (34.8%), and 18 (41.8%) isolates were resistant to amikacin, gentamicin, and tobramycin, respectively. Significant reductions in the MICs of amikacin, gentamicin, and tobramycin were observed after adding curcumin in 54-100% of aminoglycoside-resistant isolates, while fewer changes in the MICs of aminoglycosides were seen against these clinical isolates after adding PAβN (36-55%). Conclusion: Curcumin and PAβN can potentiate the effect of aminoglycosides on clinical isolates of Pseudomonas aeruginosa and change their susceptibility pattern due to efflux pump inhibition. However, our outcomes detected that curcumin was more effective than the PAβN against the aminoglycoside-resistant isolates of P. aeruginosa.