The current work aims to determine the effect of metformin on some antibiotics' efficacy against some bacterial isolates; moreover, determination of fractional inhibitory concentration (FIC) index. Six bacterial isolates (Staphylococcus aureus, Streptococcus viridans, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and E.coli) diagnosed by VITEC-2- Compact. Several metformin concentrations (100 ug, 200 ug, 300 ug, 400 ug and 500 ug) were prepared and tested for the sensitivity of selected isolates to determine the best inhibitory concentration of bacteria. Used the disc diffusion method to determine the antimicrobial activity of metformin alone and when combined with antibiotics against all isolates after preparing MIC for each antibiotic. FIC index was measured by checkerboard assays of a combination of antibiotics with metformin to determine the types of reactions. Metformin showed the best antibacterial action against the bacterial strains at a 500 μg/ml concentration, it's increased the effectiveness of the antibiotic in inhibiting bacterial isolates by the desk diffusion method with a significant difference at (P <0.05). About the FIC index, found that most of the interactions were partial synergies of 50%, metformin was recorded with amikacin as the highest reaction (partial synergy). Synergy interaction recorded in 11.11% of the tests, while additive and indifferent reactions was recorded similar rates at (16.16%), and only 5.55% of outcomes were indeterminate. Importantly, there were no antagonistic interactions between metformin and the used antibiotics. E. coli was the most bacteria that reported a synergistic reaction when metformin was combined with amikacin and gentamicin.