During the last years, infections have become a global health emergency, where the appearance of bacteria highly resistant to traditional antibiotics have set off an alarm worldwide. Moreover, the increased incidence and mortality resulting from its aggravated states, sepsis, and septic shock, have been observed with growing concern. In this context, knowing the need for a new concept for treatment, peptides such as antimicrobial peptides (AMP) and host defense peptides (HDP), have started to show interesting properties in the development of new antimicrobial agents and host response modulatory therapies. Nevertheless, since it is a well-known fact that a peptide-based drug development is a long process that consumes a significant number of resources, recent approaches that tend to mitigate these obstacles, have included the implementation of novel in silico strategies for the optimization of naturally occurring AMP and HDP. In this review, we analyze these strategies that seek to improve not only peptide design, but also production, by including the incorporation of computational biology techniques such as molecular dynamics.