Cationic antimicrobial peptides (CAMPs) have recently been associated with the progression of various human diseases, including psoriasis. Although several therapies are currently used to treat psoriasis, they present various disadvantages, such as hepatotoxicity, nephrotoxicity, and skin atrophy. A highly promising approach to overcome these limitations is the use of polyanions for selective CAMP scavenging. In this study, sulfated glycogen was developed as a novel, natural, polysaccharide-based, biodegradable complexing agent for CAMP inhibition, with potential applications in the treatment of psoriasis. The synthesized materials were characterized using various physicochemical methods. To optimize the interaction between the modified polysaccharide and CAMPs, different degrees of functionalization with anionic sulfate groups were introduced into glycogen macromolecules. This was achieved by varying two reaction parameters: the amount of sulfation agent and the reaction time. Dynamic light scattering confirmed that the prepared polymers demonstrated a strong ability to complex with the model cationic protein lysozyme at both pH 5.0 and 7.4. Notably, modified glycogens containing one sulfate group per one or three glucose units significantly reduced the hemolytic toxicity of another cationic peptide, melittin, to human red blood cells in vitro. The results indicate that these modified glycogen materials hold significant promise for future psoriasis treatment.