Background Carbapenems are the most commonly used antibiotics for severe infections induced by metallo-beta-lactamases producing Enterobacteriaceae and Pseudomonas aeruginosa. Resistance to almost all β-lactam antibiotics, including carbapenems, is conferred by metallo-β-lactamases (MBLs). Objectives Detection and inhibition of MBLs production as a promising approach to overcome resistance to carbapenems. Methods 160 clinical isolates of Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were tested for antimicrobial susceptibility by The disk-diffusion method. The ability of the isolates to produce MBL enzyme was detected phenotypically and genotypically by PCR. The potential ability of pantoprazole and omeprazole to inhibit metallo-β-lactamases (MBLs) was confirmed by real-time PCR. Results Omeprazole and pantoprazole reduced the hydrolytic activities of MBLs. Both drugs had synergistic effects with meropenem. Meropenem minimum inhibitory concentration decreased in the presence of pantoprazole (2-16) folds, and omeprazole (2-32) folds. The metallo-β-lactamases genes blaNDM, blaIMP and blaVIM were downregulated by both drugs. In silico study showed that both drugs had reasonable binding energy and revealed that omeprazole had higher binding energy and chelating activity of zinc ions of the enzymes. Conclusion The combination between meropenem and omeprazole or pantoprazole could be useful for treating infections caused by MBLs producing bacteria.