Cell-penetrating poly(disulfide)s (CPDs) can be considered as a good candidate for a general method for intracellular delivery of a substrates of interest. However, CPDs are still not fully understood and suffer from lack of ease-of-use, limiting their common application. This thesis aims to further develop CPDs by tackling their key limitations, enabling their use to solve the daily delivery problems of tomorrow. Firstly, a new dynamic conjugation was introduced to make it easier to attach substrates containing a thiol or disulfide to a CPD, at competitive rates of 1500 M^-1s^-1. Then, the mode of action of CPDs was elucidated in part, uncovering that CPDs interact mainly with protein disulfide isomerase A3 to penetrate the cells by thiol-mediated uptake. Lastly, the templated ring-opening polymerization of cyclic disulfide was attempted on an oligonucleotide template, leading to the exploration of CPDs with alternative backbones, based on thiolactone and asparagusic monomers.