ObjectiveTo systematically review the efficacy and safety of 12 antimicrobial drug regimens for the treatment of multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. MethodsThe PubMed, Cochrane Library, Web of Science, ClinicalTrials, CNKI, WanFang Data, and Chinese Medical Journal Full-text Database were electronically searched to collect studies related to objectives form inception to February 2023. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Stata software was then used to perform a network meta-analysis. ResultsA total of 64 articles were included. The network meta-analysis results indicated that combination regimens based on carbapenems, β-lactam/combination agents, or tigecycline showed higher clinical antibacterial effectiveness and bacterial clearance rates for resistant bacterial infections. Among all regimens, tigecycline + β-lactam/combination agent, polymyxin + β-lactam/combination agent, and triple-therapy regimens exhibited superior antibacterial effects. Moreover, most combination regimens containing carbapenems had lower mortality risks, with carbapenems combined with aminoglycosides, β-lactam/combination agents, or polymyxins ranking high in clinical or bacteriological efficacy. ConclusionCurrent evidence suggests that combination regimens based on β-lactam/combination agents, carbapenems, and tigecycline may be beneficial for improving the clinical and bacteriological efficacy of treating resistant bacterial infections. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.