Purpose <p>The benefits and risks of complement inhibitors for the treatment of immunoglobulin A nephropathy (IgAN) remain uncertain. We conducted this systematic review and meta-analysis to compare the efficacy and safety of complement inhibitors vs. placebo.</p> Methods <p>The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched until December 20, 2024. This study analyzed the effects of complement inhibitors on the 24-h urinary protein-to-creatinine ratio (24-h UPCR), estimated glomerular filtration rate (eGFR), and the incidence of adverse events in IgAN.</p> Results <p>In total, 4 studies with 398 patients were included in the systematic review and meta-analysis. In patients with IgAN, complement inhibitors significantly attenuated the decline in eGFR [MD = 3.50&#xa0;ml/min/1.73 m², 95% CI (0.44, 6.57),&#xa0;<i>P</i> &lt; 0.05] and demonstrated superior efficacy in reducing proteinuria markers: a 24-h UPCR reduction of −0.71&#xa0;g/g [95% CI (−0.91, −0.50),&#xa0;<i>P</i> &lt; 0.05] was observed. Safety analyses revealed comparable tolerability between the intervention and control groups, with no statistically significant difference in adverse event incidence [RR = 0.91, 95% CI (0.74, 1.11),&#xa0;<i>P</i> = 0.35].</p> Conclusion <p>Complement inhibitors appear to confer renal protective effects without increasing the risk of adverse events in patients with IgAN.</p>