The mannose receptor (MR, CD206) is a transmembrane C-type lectin receptor primarily expressed by macrophages, dendritic cells, and endothelial cells. It plays a crucial role in endocytosis and antigen processing and presentation. MR carbohydrate recognition domains (CRDs) exhibit high binding affinity for branched and linear oligosaccharides. Multivalent mannose presentation on various templates, such as peptides, proteins, polymers, micelles, and dendrimers, has been shown to be an effective approach for selective and efficient delivery of therapeutically active agents to MR. This review provides a detailed account of the synthesis and application of mannosylated bioactive formulations for MR-mediated delivery in treatments of cancer and other infectious diseases. It highlights the necessary structural features of mannose-containing ligands for successful binding to the MR. The review also discusses the structure and function of MR, the synthesis of multivalent mannosylated platforms, and the potential future perspectives for mannose-receptor targeting delivery.The mannose receptor (MR, CD206) is a transmembrane C-type lectin receptor primarily expressed by macrophages, dendritic cells, and endothelial cells. It plays a crucial role in endocytosis and antigen processing and presentation. MR carbohydrate recognition domains (CRDs) exhibit high binding affinity for branched and linear oligosaccharides. Multivalent mannose presentation on various templates, such as peptides, proteins, polymers, micelles, and dendrimers, has been shown to be an effective approach for selective and efficient delivery of therapeutically active agents to MR. This review provides a detailed account of the synthesis and application of mannosylated bioactive formulations for MR-mediated delivery in treatments of cancer and other infectious diseases. It highlights the necessary structural features of mannose-containing ligands for successful binding to the MR. The review also discusses the structure and function of MR, the synthesis of multivalent mannosylated platforms, and the potential future perspectives for mannose-receptor targeting delivery.