Human herpesviruses are among the most prevalent pathogens and currently there are no drugs available that could cure diseases induced by them. The most widely utilized antiherpes drugs, acyclovir and its derivatives, have serious limitations, such as low bioavailability and severe side effects. The current paper reports on the synthesis and characterization of cationic dextran derivatives (DEXxDSy) of various molecular weights and various degrees of substitution with ammonium groups, which were tested as antiherpes agents. DEXxDSy showed high effectiveness against HSV-1 and HSV-2 viruses, as found using a variety of techniques. Importantly, no toxicity was observed for these compounds in the range of active concentrations, demonstrating their potential as antivirals. The mechanism of action of DEXxDSy was assessed. We hypothesize that they may limit virus transmission, as extensive examination showed that they hamper the interaction between the virus and the cellular attachment receptor.