C-reactive protein (CRP) is a highly conserved pentraxin, synthesized primarily in the liver, and is widely recognized as a highly sensitive biomarker for inflammation and tissue damage. While considerable research has focused on elucidating the structural and functional aspects of CRP, along with its utility as a biomarker reflecting disease severity and activity, the understanding of distinctive CRP structural isoforms is evolving. Its role is not only as a biomarker but also as a regulator of both physiologic and pathophysiologic processes of inflammation and autoimmune pathology. In this review, we systematically reviewed the role of CRP and its monomeric form, mCRP, in autoimmune disorders like inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. It investigates their impact on immune dysregulation, tissue damage, and disease progression. The review also discusses studies suggesting CRP and mCRP as potential therapeutic targets to manage inflammation and maintain immune balance in autoimmune diseases and provide insights for future research and therapeutic approaches in autoimmune disease management.