A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-1,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed. A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo [de] isochromene-1, 3-dione. All the new body of reactant was analyzed by NMR, IR, MS and HRMS spectra. The antimicrobial activities were fractionated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay showed that most of the prepared compounds showed inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values ​​of the target molecules were also preliminarily incorporated.