Peptides as drug candidates have the prior of biocompatibility (compare with small molecular) and easy manual synthesis (compare with protein), while peptide also have the shortcomings of short half-life, conformation flexible, poor cell permeability. To conquer these many peptide modification methods were developed. Side-chain cyclization developed in the past several decades was wildly used now days and have been proved can neutralize these shortcomings. While till now only a few methods such as RCM was wildly used for the side-chain formation. For variable side-chain modifications new facile side-chain formation methods were needed. Our group has developed several methods which can easily insert heteroatom on most of the position of a hydrocarbon side-chain. And we have proved through serum and mouse digestion that this kind of side-chain on short peptide can highly enhance peptide’s stability and CD result show this method also have some efficacy in peptides alpha-helix conformation stabilization.