Selenoxo amide groups have never been incorporated inte peptides previously. Here, the selenoxo peptides have been synthesized for the first time. The selenoxo peptide bond can be efficiently photoswitched from trans conformation to cis by irradiation at about 290 nm. The cis conformation is quite stabil, with a life time from hours to days depending on peptide sequence. Additionally, an autocatalytic rapid nitrogen inversion pathway has been found to contribute to the accelerated cis to trans decay of the selenoxo peptide bond in basic aqueous solution. Moreover, the atomic polarizability is found to play a dominant role in determining the electronic effects of chalcogen substitution. Collectively, the selenoxo peptide bond is an efficient photoswitch for the peptide conformational photocontrol and the special electronic effects of selenoxo modulation allows it to be applied to probe the noncovalent interactions in peptides and proteins.