Naturally occurring β-turns are important in mediating protein folding, receptor binding interactions as well as in serving as sites for post-translational modification in proteins.^1-3 Therefore, the development of novel β-turn mimetics is of fundamental interest as well as aid in providing novel frameworks for drug design. Non-protein amino acids bearing N-methylation, α,α-dialkylation or D-configurations have been found to induce b-turns and stabilize b-hairpin conformations in synthetic peptides.^4-6 Despite these literature efforts, the realization of designed β-hairpin peptides with biological activities and the use of novel b-turns to facilitate the syntheses of cyclic tetrapeptides remains relatively less documented and present several challenges. Our recent research developed a novel β-turn scaffold, that permits the pre-organization of designed linear tetrapeptides and facilitate their cyclization to yield synthetically challenging cyclic tetrapeptides (CTPs) in quantitative yields.⁷ Parameters such as solvent polarity and ring dissection were investigated during the syntheses of the CTPs resulting in optimized synthetic strategies with significant improvements to product yields than previously reported.^7,8 The designed β-turn was also incorporated in analogues of naturally occurring β-hairpin antimicrobials and de novo designed peptides resulting in synthetic analogues with altered molecular architecture and providing broad-spectrum β-hairpin antimicrobial peptides with enhanced therapeutic window.⁹ Further investigations have now allowed us to fine-tune the amino acid sequences for engineering acyclic and cyclic antimicrobial peptides that adopt β-hairpin structures. A summary of these findings that include chemical syntheses, structural analyses and bioactivity studies will be presented.