The properties of modified biomaterial are gaining more and more importance in drug delivery systems. Sialic acid (SA) and polysialic acid (PSA) serve as endogenous substances, which are non-immunogenic and biodegradable. At the same time, SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain; PSA modification can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood, thus achieving active targeting effect. These properties offer a variety of opportunities for applications in drug delivery systems. This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs, proteins and carriers in drug delivery systems.