Antibiotic resistance is rapidly increasing, and new anti-infective therapies are urgently needed. In this regard, antimicrobial peptides (AMPs) may represent potential candidates for the treatment of infections caused by multiresistant microorganisms. In this narrative review, we reported the experience of our research group over 20 years. We described the AMPs we evaluated against Gram-positive, Gram-negative, and fungi. In conclusion, our experience shows that AMPs can be a key option for treating multiresistant infections and overcoming resistance mechanisms. The combination of AMPs allows antibiotics and antifungals that are no longer effective to exploit the synergistic effect by restoring their efficacy. A current limitation includes poor data on human patients, the cost of some AMPs, and their safety, which is why studies on humans are needed as soon as possible.
