Diabetes mellitus is a major health problem that affects approximately million people globally. One of its most severe complications is the development of diabetic foot ulcers DFU . Ischemic and neurophatic lesions are of major importance for DFU onset however, it is the infection by multidrug-resistant and biofilm-producing microorganisms, along with local microenvironmental conditions unfavorable to antibiotics action that ultimately cause infection chronicity and lower limbs amputation. Novel therapeutic protocols for DFU management are extremely urgent. "acteriophages, probiotics and antimicrobial peptides "MP have recently been proposed as alternatives to currently available antibiotics. "acteriophages are viruses that specifically infect and multiply within bacterial cells. Their ability to diffuse through polymeric matrixes makes them particularly efficient to eradicate biofilmbased bacteria. Promising results were also observed with probiotic therapy. Probiotics are well-characterized strains with the ability to compete with pathogenic microorganisms and modulate the host immune response. "MP are molecules produced by living organisms as part of their innate immune response. Unlike conventional antibiotics, "MP also act as immunomodulators and resistance to "MP was rarely observed, supporting their potential as therapeutic agents. These innovative therapeutic strategies may in the future substitute or complement antibiotherapy, ultimately contributing for the decrease in multidrug-resistant bacteria dissemination.