Abstract: In gene therapy, natural polymer polysaccharides have been considered as good gene delivery materials due to their good biocompatibility and high tunability. As two of important natural polymer polysaccharides, chitosan and dextran, as well as their derivatives, have been widely used as carrier materials for gene-based therapeutics. A variety of methods have been developed to modify chitosan and dextran, expanding their applications in gene delivery. In this review, the structure and properties of chitosan and dextran are introduced, followed by the recent research progress on the application of modified chitosan and dextran in gene delivery. Finally, one prospect of their future development is proposed.