Discovery of peptides used in protein therapeutics proposes treatment for a wide range of infectious and chronic human diseases. Therapeutically significant peptides are developed from naturally occurring peptides or through de novo design. The characteristic features like small size, high stability and structural compatibility with target proteins identifies peptides as a potential class of drug and novel antibiotics. Recent acceptance of computer-aided drug design involving computational methods and resources for design and discovery of new therapeutic solutions has rapidly increased. This review describes systematic identification of the most imperative data sources and computational applications in designing peptides with desired biological features and enhanced therapeutic importance in pharmaceutical and nanomedicine firm. In addition, the current challenges for designing a stable peptide with favorable physiologic properties and the ways to overcome these issues are discussed with successful examples from literature. Using this approach, several peptides having anti-cancer, anti-angiogenic, anti-inflammatory and anti-microbial activities have been designed and biologically characterized. Copyright © 2016 American Scientific Publishers.