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Curcumin and triangular silver nanoplates (TSNP)-incorporated bacterial cellulose (BC) films present an ideal antimicrobial material for biomedical applications as they afford a complete set of requirements, including a broad range of long-lasting potency and superior efficacy antimicrobial activity, combined with low toxicity. Here, BC was produced by <i>Komagataeibacter medellinensis</i> ID13488 strain in the presence of curcumin in the production medium (2 and 10%). TSNP were incorporated in the produced BC/curcumin films using ex situ method (21.34 ppm) and the antimicrobial activity was evaluated against <i>Escherichia coli</i> ATCC95922 and <i>Staphylococcus aureus</i> ATCC25923 bacterial strains. Biological activity of these natural products was assessed in cytotoxicity assay against lung fibroblasts and in vivo using <i>Caenorhabditis elegans</i> and <i>Danio rerio</i> as model organisms. Derived films have shown excellent antimicrobial performance with growth inhibition up to 67% for <i>E. coli</i> and 95% for <i>S. aureus</i>. In a highly positive synergistic interaction, BC films with 10% curcumin and incorporated TSNP have shown reduced toxicity with 80% MRC5 cells survival rate. It was shown that only 100% concentrations of film extracts induce low toxicity effect on model organisms’ development. The combined and synergistic advanced anti-infective functionalities of the curcumin and TSNP incorporated in BC have a high potential for development for application within the clinical setting.