The cell-penetrating poly(disulfide)s (CPDs) developed by the Matile group in 2013 have shown excellent cellular uptake properties. Indeed, their mechanism of cell entry relies on the interaction with exofacial anions and thiols, due to the presence in their sidechain of guanidinium groups and in their backbone of disulfides, respectively. Therefore, their uptake is counterion- and thiol-mediated and the combination of the two has enabled the delivery of model fluorophores as well as proteins, antibodies and quantum dots. In order to study the effect of modifications in the CPD structure, new monomers need to be sythesized and then polymerized, through disulfide-exchange, with conditions that need to be optimized each time for even the smaller changes in the monomer structure. This, therefore, called for the development of a strategy that would allow to install different functionalities starting form the same batch of polymer. In the first approach, hydrazone exchange was envisioned as a strategy to perform CPD sidechain functionalization. Due to the low yield of functionalization that was obtained, we decided to adopt a more robust strategy, that is copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Indeed, by preparing an azide polymer, CuAAC could be performed with different alkynes to obtain modified CPDs with excellent yields, reproducibility and versatility. Glycosylation was successful to improve the cellular uptake by integrating a new mechanism to the mode of action of the CPDs. It also enabled the efficient delivery of streptavidin by performing glycosylation at the sidechain of biotinylated polymers. The compatibility of CuAAC with the poly(disulfide) backbone of the polymers was also exploited for terminator engineering.