In 2019, König's group reported a general decarboxylative photosubstitution of dicyanobenzene-based photocatalysts under blue light irradiation. The alkyl radical, generated through decarboxylation, can be trapped by the radical anion formed after reduction of the photocatalyst. The substituted products are formed after a subsequent cyanide elimination. The monocyanobenzene products are still blue TADF emitters and reducing photocatalysts. However, amino acids or peptides have not been used as carboxylic acid partners in this transformation. During our studies on the decarboxylative alkynylation of peptide C-termini, we also observed decarboxylative photosubstitution products between amino acids/peptides and 4CzIPN, which motivated us to optimize this transformation. Gratifyingly, the radical substitution could be achieved by simply shedding blue light on a mixture of peptide, 4CzIPN and K2CO3 for model substrate 3aa (see Table in Supporting Information for reaction optimization). To assess the generality of our method, we first investigated systematically different amino acids on smaller tetrapeptides bearing a Pro at the C-terminus, which has been reported to be the most efficient amino acid for decarboxylative functionalization (Figure , 3aa-3pa). Arg (3ba), Met (3ca), Asp (3da), amides (3ea, 3fa), Lys (3ga), alcohols (3ha, 3ia), a terminal alkyne (3ja) as well as Tyr (3pa) were all tolerated, resulting in 24-81% yield of the corresponding products. Trp (3ka) was not compatible with the photoredox conditions due to its susceptibility to oxidation. We then expanded our investigation to different C-terminal amino acids (products 3la-3oa). Glu and pipecolic acid could be converted to the desired decarboxylation products 3ma and 3oa in 20% and 46% yield, under the same reaction conditions. For Ala (3la) and Phe (3na), it was necessary to use a stronger 440 nm Kessil lamp. This modification significantly improved the conversion of peptides, although it also led to more degradation of 4CzIPN. Encouraged by the excellent functional group tolerance and chemoselectivity of the transformation, we applied it to more complex peptides (Figure , 3pa-3ya). β-casomorphin (1-4), containing a free Tyr and N-terminus, was transformed into conjugate 3pa in 52% yield. Decamer 1q, with a free Glu residue, was selectively functionalized at the C-terminus, yielding 3qa exclusively. Other successfully modified bioactive peptides include an v3 integrin binding cyclic peptide (3ra), myelin basic protein fragment 87-99 (3sa), which induces T cell proliferation, TRAP-7 (3ta), a thrombin receptor activator, a fibronectin binding inhibitor (3ua) and the neurotransmitter substance P (3va). We also synthesized conjugates 3wa-3ya starting from three cell-penetrating peptide sequences (VPALK, AAVLLPVLLAA and (KFF)3K ) with different length and hydrophilicity with added Pro at C terminus to facilitate reaction with 4CzIPN. Finally, we extended this reaction to other Cz(I)PN derivatives. 4ClCzIPN (2b) and 3CzClIPN 37 (2c) were converted to products 3ab, 3yb and 3ac in 20-51% yield. Although 2CzPN (2d) exhibited lower reactivity due to weak absorption under blue light irradiation, the yield significantly improved upon switching the light source from 467 nm strips to a 390 nm Kessil lamp. Additionally, a chiral BINOL-derivative 2e, known as a TADF emitter for circularly polarized light emission, yielded conjugate 3ae in 56% yield.