Over the past two decades, significant efforts have invested in the development of strategies for the stabilization of macrocyclic peptides with α-helix structure by stapling their architectures. These strategies can be divided into two categories: side chain to side chain cross-linking and N-terminal helix nucleation. These stable macrocyclic peptides have been applied in PPI inhibitors and self-assembly materials. Compared with unmodified short peptides, stable α-helix macrocyclic polypeptides have better biophysical properties including higher serum stability, cell permeability, and higher target affinity. This chapter will systematically introduce approaches for helical stabilization of peptide macrocycles, such as ring-closing metathesis (RCM), lactamisation, cycloadditions, reversible reactions, thioether formation as well as newly found sulfonium center formation and the common use of helical stabilized macrocyclic peptides.