In this study, we characterized the influence of polycation chemistry and valency on DNA protection in the condensed state against free radical oxidation. Potential mechanisms of DNA protection could include DNA compaction by polycations, cation binding to DNA, and/or radical scavenging by polycations. The latter scenario would result in the formation of radical polycations, thereby sparing the DNA from damage. However, there is also evidence that peptide radicals may be a route to transfer damage to DNA in the compacted state. Although the peptide radical model was not extensively tested in this study, our previous in vitro antioxidant scavenging experiments (unpublished) have indicated negligible antioxidant activities for protamines. This suggests that radical scavenging does not adequately account for the observed DNA protection in these polyplexes. This hypothesis is further supported by our findings that higher nitrogen-to-phosphate (N/P) ratios for protamine-DNA and other polyplexes, where more unbound polycation chains are available to interact with free radicals, did not significantly modify DNA damage levels within the condensed phase. We propose that DNA condensation could protect polyplex DNA by limiting the access of free radicals to the DNA helices within the condensate. To investigate potential steric effects, we employed different polycations to achieve variable DNA packaging densities and quantified DNA damage directly within the condensed phase.