Objective <p>Autoimmune diseases (AIDs) are a spectrum of chronic conditions characterized by abnormal immune responses directed against the body’s own tissues. Current therapeutic strategies still rely on broad-spectrum immunosuppression, which often produces severe adverse effects and is ineffective in targeting comorbidities. The complement system, a key component of innate immunity, has been increasingly recognized for its role in the pathogenesis and progression of AIDs. This review aims to assess the diagnostic and therapeutic potential of targeting the complement system in AIDs.</p> Methods <p>A comprehensive literature review was conducted using the PubMed, Medscape, and ClinicalTrials.gov databases. The analysis included both original research and review articles, as well as data from ongoing and completed clinical trials focused on complement-targeted therapies.</p> Results <p>Complement activation contributes to inflammation, tissue injury, and amplification of adaptive immunity in AIDs. Current and emerging complement-targeted therapies, including monoclonal antibodies and small-molecule inhibitors has shown promising preliminary outcomes in reducing disease activity with fewer adverse effects.</p> Conclusion <p>Targeting the complement system represents a promising and more precise strategy for the treatment of AIDs. Ongoing clinical evaluation is essential to establish its long-term safety and efficacy, with the potential to significantly advance future therapeutic approaches.</p>