ObjectivesTo investigate the antimicrobial efficacy of Melittin (MEL) against carbapenem-resistant Acinetobacter baumannii isolates as a potential alternative treatment option.Materials and methodsMinimum Inhibitory Concentrations (MICs) of MEL, imipenem (IMP), and meropenem (MER) were evaluated through the microdilution method in 10 resistant isolates. Synergistic interactions were assessed using checkerboard, time-kill assays, and an in vivo Galleria mellonella model.ResultsMEL MICs ranged from 31.25-62.5 mg/L. Only the M5 isolate showed synergy with both combinations. Fractional Inhibitory Concentration Index (FICI) values were 0.375 for MEL+MER and 0.5 for MEL+IMP. Larvae treated with MEL combinations had increased survival rates compared to the infection group.ConclusionsMEL appears to be a promising therapeutic candidate against carbapenem-resistant A. baumannii, and its combination with carbapenems may enhance in vivo efficacy.