An efficient method for the direct labeling of the Arg guanidinium group in native peptides is reported. This straightforward procedure allows modifying the arginine moiety in peptides with various reporter groups, such as fluorophores, biotin, etc., under mild conditions in an operationally simple procedure. The scope of this method tolerates various functionalized amino acids such as His, Ser, Trp, Tyr, Glu, etc., while the only limitations uncovered so far are restricted to cysteine and free amine residues. The utility of this late-stage diversification method was demonstrated in direct labeling of leuprolide, a clinically used drug, for distribution monitoring in Daphnia, and in labeling of microcystin, a cyanobacterial toxin.