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<i>Pseudomonas aeruginosa</i> is notorious for its ability to develop a high level of resistance to antimicrobial agents. Resistance-nodulation-division (RND) efflux pumps could mediate drug resistance in <i>P. aeruginosa</i>. The present study aimed to evaluate the antibacterial and anti-efflux activities of cinnamon essential oil either alone or combined with ciprofloxacin against drug resistant <i>P. aeruginosa</i> originated from human and animal sources. The results revealed that 73.91% of the examined samples were positive for <i>P. aeruginosa</i>; among them, 77.78% were of human source and 72.73% were recovered from animal samples. According to the antimicrobial resistance profile, 48.73% of the isolates were multidrug-resistant (MDR), 9.2% were extensive drug-resistant (XDR), and 0.84% were pan drug-resistant (PDR). The antimicrobial potential of cinnamon oil against eleven XDR and one PDR <i>P. aeruginosa</i> isolates was assessed by the agar well diffusion assay and broth microdilution technique. The results showed strong antibacterial activity of cinnamon oil against all tested <i>P. aeruginosa</i> isolates with inhibition zones’ diameters ranging from 34 to 50 mm. Moreover, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of cinnamon oil against <i>P. aeruginosa</i> isolates ranged from 0.0562–0.225 µg/mL and 0.1125–0.225 µg/mL, respectively. The cinnamon oil was further used to evaluate its anti-efflux activity against drug-resistant <i>P. aeruginosa</i> by phenotypic and genotypic assays. The cartwheel test revealed diminished efflux pump activity post cinnamon oil exposure by two-fold indicating its reasonable impact. Moreover, the real-time quantitative polymerase chain reaction (RT-qPCR) results demonstrated a significant (<i>p</i> < 0.05) decrease in the expression levels of <i>MexA</i> and <i>MexB</i> genes of <i>P. aeruginosa</i> isolates treated with cinnamon oil when compared to the non-treated ones (fold changes values ranged from 0.4204–0.7474 for <i>MexA</i> and 0.2793–0.4118 for <i>MexB</i>). In conclusion, we suggested the therapeutic use of cinnamon oil as a promising antibacterial and anti-efflux agent against drug-resistant <i>P. aeruginosa</i>.