Viral outbreaks are a topic of worldwide concern, resulting in a significant impact in health systems, a large number of deaths, and huge economical losses. The damage caused by Covid-19 has further highlighted the importance of prospecting for new molecules that can be applied in the prevention and treatment of viral infections. Many studies describe the remarkable antimicrobial activity of lipopeptides produced by Bacillus spp., especially against fungi and bacteria. However, research regarding the antagonistic effects on viruses is less frequent. Despite that, the antiviral activity of lipopeptides produced by Bacillus spp. has been demonstrated, indicating that these molecules could be potential candidates to control viral diseases. In this article, a compilation of reports with consistent data regarding the antiviral effect of Bacillus lipopeptides and the mechanisms involved in this process are presented. Moreover, the immunomodulatory role and toxicity profile of these molecules are discussed. Bacillus lipopeptides may exert an indirect antiviral effect, since they are able to positively induce humoral and cell-mediated immune responses. Moreover, their antiviral effect was observed in vitro and in vivo at nontoxic concentrations, offering a safe perspective for possible clinical application of these molecules. Finally, the challenges related to optimization and increasing production yield are addressed. This is the first critical review dedicated exclusively to antiviral activity of Bacillus lipopeptides.