Dehydroalanine (Dha) residues are attractive non-canonical amino acids that occur naturally in ribosomally synthesised and post-translationally modified peptides (RiPPs). Dha residues are attractive targets for selective late-stage modification of these complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobial peptide nisin and in the proteins Small Ubiquitin-like Modifier (SUMO) and superfolder Green Fluorescent Protein (sfGFP). For this purpose, a new water-soluble iridium(III) photoredox catalyst was used. The design and synthesis of this new photocatalyst, [Ir(dF(CF3 )ppy)2 (dNMe3 bpy)]Cl3, is presented. In contrast to commonly used iridium photocatalysts, this complex is highly water-soluble and allows modification of peptides and proteins in water and aqueous solvents under physiologically relevant conditions and with short reaction times and low reagent and catalyst loadings. This work suggests that photoredox catalysis using this newly designed catalyst is a promising strategy to modify dehydroalanine-containing natural products and thus may have great potential for novel bioconjugation strategies.