Mannose ligands for targeting the mannose receptor (MR) are crucial for efficient delivery of therapeutically active agents to MR-expressing cells, such as macrophages and dendritic cells. The MR, a C-type lectin receptor, recognizes and binds to glycosylated ligands, particularly those ending in mannose, fucose, or N-acetylglucosamine. Multivalent mannose presentation on various carriers, including liposomes, nanoparticles, and dendrimers, enhances binding efficiency and selectivity. Recent studies highlight the importance of structural features of mannose-containing ligands for effective MR binding. The MR's CRD4 domain binds linear and branched carbohydrates, with branched structures showing higher affinity. The binding affinity is influenced by the arrangement and spacing of mannose units, as well as the linkage between the carrier and the mannose derivative. Copper-catalyzed click reactions and amine-carboxylic acid reactions are used for ligand attachment. Mannosylation of peptides and antigens improves antigen presentation and T-cell activation, making it a valuable strategy for vaccine development. Mannose-based ligands, such as synthetic glycol-adjuvants and mannosylated liposomes, enhance immune responses and target specific cells. Mannose-modified liposomes and nanoparticles show promise in cancer therapy by targeting macrophages and dendritic cells. The use of mannosylated carriers, including liposomes, nanoparticles, and polymers, improves drug delivery and therapeutic outcomes. These systems are effective in targeting MR-expressing cells, enhancing drug uptake, and modulating immune responses. The review emphasizes the importance of structural and functional modifications of mannose ligands for optimal MR targeting and therapeutic applications.Mannose ligands for targeting the mannose receptor (MR) are crucial for efficient delivery of therapeutically active agents to MR-expressing cells, such as macrophages and dendritic cells. The MR, a C-type lectin receptor, recognizes and binds to glycosylated ligands, particularly those ending in mannose, fucose, or N-acetylglucosamine. Multivalent mannose presentation on various carriers, including liposomes, nanoparticles, and dendrimers, enhances binding efficiency and selectivity. Recent studies highlight the importance of structural features of mannose-containing ligands for effective MR binding. The MR's CRD4 domain binds linear and branched carbohydrates, with branched structures showing higher affinity. The binding affinity is influenced by the arrangement and spacing of mannose units, as well as the linkage between the carrier and the mannose derivative. Copper-catalyzed click reactions and amine-carboxylic acid reactions are used for ligand attachment. Mannosylation of peptides and antigens improves antigen presentation and T-cell activation, making it a valuable strategy for vaccine development. Mannose-based ligands, such as synthetic glycol-adjuvants and mannosylated liposomes, enhance immune responses and target specific cells. Mannose-modified liposomes and nanoparticles show promise in cancer therapy by targeting macrophages and dendritic cells. The use of mannosylated carriers, including liposomes, nanoparticles, and polymers, improves drug delivery and therapeutic outcomes. These systems are effective in targeting MR-expressing cells, enhancing drug uptake, and modulating immune responses. The review emphasizes the importance of structural and functional modifications of mannose ligands for optimal MR targeting and therapeutic applications.