Peptides are important biomolecules in drug development with their high specificities to their targets. Many peptide-based drug candidates have been increasingly involved in clinical and preclinical studies. Unfortunately, peptides have some disadvantages such as poor metabolic stability, poor oral bioavailability and high production costs. These problems can be overcome by modifications that have been inspired from highly stable disulfide-rich peptides already found in nature. This review describes the structure and bioactivity of disulfide-rich peptides and their development with various modifications to become candidate molecules in drug design and development studies.