Herein we report the first example of a strategy for peptide functionalization through the generation of selenocysteine electrophile in 5- and 6-endo-dig cyclization reactions. This simple approach allows bio-conjugation of selenocystine-based peptides. The developed protocol is based on copper(II) bromide mediated reactions of selenocystine with either 2-propargyl N-heterocycles through 5-endo-dig closure or with 2-ethynylbiaryls through 6-endo-dig closure. It allows construction of indolizinium moiety on selenocysteine residue as well as formation of polyaromatic fragment bonded to selenium in a simple one-pot process under mild reaction conditions.