Bioactive peptides participate in numerous metabolic functions of living organisms and have emerged as potential therapeutics on a diverse range of diseases. Albeit peptide design does not go without challenges, overwhelming advancements on in silico methodologies have increased the scope of peptide-based drug design and discovery to an unprecedented amount. Within an in silico model versus an experimental validation scenario, this review aims to summarize and discuss how different in silico techniques contribute at present to the design of peptide-based molecules. Published in silico results from 2014 to 2018 were selected and discriminated in major methodological groups, allowing a transversal analysis, promoting a landscape vision and asserting its increasing value in drug design.