Dengue virus (DENV) is an arbovirus that belongs to the Flaviviridae family. Studies reveal that peptides secreted by amphibians have many functions, such as antiviral and antimicrobial activities. As there is no antiviral drug effective against the DENV, the antiviral activity of a synthetic peptide called HS-1, derived from the secretion of the anuran Hypsiboas semilineatus, has been evaluated. The assays of neutralization in the Vero cells show a complete inhibition of infection of the serotypes 2 and 3. Furthermore, the direct action of peptides on the viral particle can be observed through atomic force microscopy. In vivo tests display 80% protection against the dengue-2 virus due to the presence of HS-1, which reveals its potential as an antiviral against the DENV. •The use of antimicrobial peptides (AMPs) as antivirals has increased in recent times and has shown promise.•Many molecules have been described as being able to inhibit viral replication, such as, analogs of defensins, dermaseptins, and latarcins.•On account of the lack of a vaccine and treatment against the dengue virus, it has been considered necessary to test antivirals against the dengue virus.•The results are promising against dengue-2 and dengue-3 and the antivirals tested have shown efficiency in both in vitro and in vivo experiments, in which the antiviral appears to act directly on the viral particle, disrupting the lipoprotein envelope.