The development of new synthetic technologies for the targeted modification of proteinogenic amino acids has been an enduring goal for peptide and protein chemists. However, our growing understanding of the enormous array of structural and functional diversity incorporated into ribosomally-synthesized and post-translationally modified peptides (RiPPs)¹ as well as non-ribosomal peptides² has provided new inspiration for the modification of naturally-occurring, albeit “non-canonical”, functional groups. Among the most enticing functionalities are N,S-acetals, which Nature beautifully incorporates into a variety of intriguing peptide scaffolds. This presentation will highlight our development of synthetic strategies for the preparation of peptide N,S-acetals,³ along with enabling synthetic tools, including electrochemical technologies,⁴ which leverage their unique reactivity.