Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields Antonio Moretta 1† , Carmen Scieuzo 1,2† , Anna Maria Petrone 1† , Rosanna Salvia 1,2† , Michele Dario Manniello 1 , Antonio Franco 1,2 , Donatella Lucchetti 3 , Antonio Vassallo 1 , Heiko Vogel 4 , Alessandro Sgambato 3,5 * and Patrizia Falabella 1,2 * 1 Department of Sciences, University of Basilicata, Potenza, Italy, 2 Spinoff XFlies s.r.l, University of Basilicata, Potenza, Italy, 3 Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy, 4 Department of Entomology, Max Planck Institute for Chemical Ecology, Jena, Germany, 5 Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, Italy Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications. Keywords: drug-resistant microorganisms, antimicrobial peptides, biomedical and pharmacological applications, pharmacokinetics and pharmacodynamics, drug delivery Abbreviations: ACE, Angiotensin-Converting Enzyme I; AMP, Antimicrobial Peptide; APD, Antimicrobial Peptide Database; API, Active pharmaceutical ingredient; DDS, Drug Delivery System; Di-Phe, di-phenylalanine; EGFR, Epidermal Growth Factor Receptor; EPL, ϵ-poly-L-lysine; GMO, Glyceryl Monooleate; HBBD, HG-Based Burn Dressings; hBD, Human b defensin; HG, Hydrogel; IPTG, Isopropyl b- D-1-Thiogalactopyranoside; LPS, Lipopolysaccharides; MRSA, Methicillin- resistant Staphylococcus aureus; PD, Pharmacodynamics; PK, Pharmacokinetics; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SCID, Severe Combined Immunodeficiency; TLR, Toll-like receptor; WHO, World Health Organization; BPS, block polymeric structure; CB, cubosome; CMC, Critical Micelle Concentration; PA, peptide amphiphiles; SPPS, Solid Phase Peptide Synthesis. Frontiers in Cellular and Infection Microbiology | www.frontiersin.org June 2021 | Volume 11 | Article 668632 1 Edited by: Francesc Rabanal, University of Barcelona, Spain Reviewed by: Surajit Bhattacharjya, Nanyang Technological University, Singapore Clara Balleste, Instituto Salud Global Barcelona (ISGlobal), Spain *Correspondence: Patrizia Falabella patrizia.falabella@unibas.it Alessandro Sgambato alessandro.sgambato@crob.it † These authors have contributed equally to this work and share first authorship Specialty section: This article was submitted to Clinical Microbiology, a section of the journal Frontiers in Cellular and Infection Microbiology Received: 16 February 2021 Accepted: 10 May 2021 Published: 14 June 2021 Citation: Moretta A, Scieuzo C, Petrone AM, Salvia R, Manniello MD, Franco A, Lucchetti D, Vassallo A, Vogel H, Sgambato A and Falabella P (2021) Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields. Front. Cell. Infect. Microbiol. 11:668632. doi: 10.3389/fcimb.2021.668632 REVIEW published: 14 June 2021 doi: 10.3389/fcimb.2021.668632