Therapeutic application of nucleic acids requires their encapsulation in nanosized carriers that enable safe and efficient intracellular delivery. Before the desired site of action is reached, drug-loaded nanoparticles (nanomedicines) encounter numerous extra- and intracellular barriers. Judicious nanocarrier design is highly needed to stimulate nucleic acid delivery across these barriers and maximize the therapeutic benefit. Natural polysaccharides are widely used for biomedical and pharmaceutical applications due to their inherent biocompatibility. At present, there is a growing interest in applying these biopolymers for the development of nanomedicines. This review highlights various polysaccharides and their derivatives, currently employed in the design of nucleic acid nanocarriers. In particular, recent progress made in polysaccharide-assisted nucleic acid delivery is summarized and the specific benefits that polysaccharides might offer to improve the delivery process are critically discussed.