Drug nanodelivery systems (DNDSs) are fascinated cargos to achieve outstanding therapeutic results of various drugs or natural bioactive compounds owing to their unique structures. The efficiency of several pharmaceutical drugs or natural bioactive ingredients is restricted because of their week bioavailability, poor bioaccessibility and pharmacokinetics after orally pathways. In order to handle such constraints, usage of native/natural polysaccharides (NPLS) in fabrication of DNDSs has gained more popularity in the arena of nanotechnology for controlled drug delivery to enhance safety, biocompatibility, better retention time, bioavailability, lower toxicity and enhanced permeability. The main commonly used NPLS in nanoencapsulation systems include chitosan, pectin, alginates, cellulose, starches, and gums recognized as potential materials for fabrication of cargos. Herein, this review is centered on different polysaccharide-based nanocarriers including nanoemulsions, nanohydrogels, nanoliposomes, nanoparticles and nanofibers, which have already served as encouraging candidates for entrapment of therapeutic drugs as well as for their sustained controlled release. Furthermore, the current article explicitly offers comprehensive details regarding application of NPLS-based nanocarriers encapsulating several drugs intended for the handling of numerous disorders, including diabetes, cancer, HIV, malaria, cardiovascular and respiratory as well as skin diseases.Copyright © 2020 Elsevier B.V. All rights reserved.