The inhibitory signal loss in the immune system is one of the important causes of autoimmunity. The Sialic acid-recognizing Immunoglobulin Superfamily Lectins or shortly "Siglecs" are cell surface proteins that are substantially expressed in hematopoietic cells. The vast majority of these proteins are expressed in the immune system cells, and are attached to sialic acid-containing ligands and act as an inhibitory receptor. These receptors produce inhibitory signals that contribute to the inactivation of the immune system cells and protect the organism from autoimmunity. Siglecs are expressed on T lymphocytes, particularly B lymphocytes and studies targeting the use of Siglecs as therapeutic agents due to their role in immune regulation are increasing rapidly. Hence, this review summarizes the structural features of sialic acid as well as role of Siglecs in autoimmunity in conjunction with their function in B and T lymphocytes as a sialic acid binding receptor, and also use of Siglecs as therapeutic agents.