question: Human defensins are a class of antimicrobial peptides, belonging to the innate immunity system. These peptides are expressed at the level of respiratory tract (both upper and lower) where they represent the first line of defense against pathogens; they are also known for their activity against different viruses, acting through diverse mechanisms, including direct binding to the virus, inhibition of viral replication, and aggregation of virions. It has been recently reported they are also effective against SARS-CoV-2. Moreover, they influence the immune response stimulating it in the challenge against microorganisms. An intriguingly potential application of defensin is related to their use as vaccine adjuvants; indeed, some in silico studies suggested their efficacy in boosting the immune response. Since the long-term persistence of acquired immunity against SARS-CoV-2 triggered by the currently employed vaccines is not known, natural agents with enhancing effects, such as defensins, administered with the vaccine, can be an interesting and attractive alternative.