Recently, natural products have been further evaluated as sources of antimicrobial agents with efficacies against a variety of microorganisms. This study reports the antimicrobial activities of pomegranate rind extract (PRE) in combination with Fe(II) and Cu(II) salts against extended-spectrum multidrug-resistant Pseudomonas aeruginosa. Antimicrobial suspension assays were carried out using aqueous extract of pomegranate alone or in combination with metals salts against P. aeruginosa. The extract:metal salt combination was also enhanced with the addition of vitamin C. Marked activities were observed for the aqueous PRE/Cu(II) preparations, which were greatly enhanced by the addition of the reductant vitamin C. In contrast, the aqueous PRE/Fe(II) preparations were inactive, regardless of addition of vitamin C. The combination of PRE and Cu(II) salts and vitamin C showed the greatest activity against clinical isolates of P. aeruginosa. These results warrant further investigation of PRE as a potential source of new antimicrobial agents.