Scavenger receptors (SRs) belong to a large receptor family expressed on immune and non- immune cells. Initially, SRs are regarded as removers able to recognize and clear modified lipoproteins; However, it is now realized that they are pattern recognition receptors (PRRs) that identify damage-associated molecular pattern (DAMP) and pathogen-associated molecular patterns (PAMPs). The wide range of ligands that bind to SRs demonstrates their diverse functions, including pathogen clearance, lipid transport, cellular differentiation, and signaling pathway activation. Previous studies have revealed the significance of SRs in regulating innate immunity and adaptive immunity. Recently, a large body of evidence further indicates the involvement of SRs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D) and inflammatory bowel disease (IBD). In this comprehensive review, we will summarize molecular structure and immunological functions of different types of SRs, and discuss the recent insights into the involvement of SRs in the development and pathogenesis of autoimmune diseases and their clinical implications and therapeutic potential.