Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness worldwide. Wet AMD (wAMD) is the primary type of AMD leading to blindness, characterized by rapid vision loss due to neovascularization. Currently, the primary treatment for wAMD relies on anti-vascular endothelial growth factor (VEGF) drugs. However, some patients respond poorly to this therapy, suggesting a complex pathogenesis that necessitates the exploration of multi-target therapeutic strategies. Recent studies have revealed that aberrant activation of the complement system plays a crucial role in the development of wAMD. Specifically, molecules such as C3, C5, C3a, C5a, and the membrane attack complex (MAC) are involved in the formation of choroidal neovascularization (CNV) by modulating VEGF and other inflammatory factors. Genetic studies have confirmed a strong association between mutations in complement-related genes and wAMD, such as CFH and C3. Furthermore, animal experiments support the therapeutic potential of complement inhibitors in treating CNV. Currently, clinical trials targeting complement components like C3, C5, and MAC are underway, with some drugs having advanced to phase II/III clinical studies. However, their efficacy requires further validation. In the future, complement-targeted therapy, particularly in combination with anti-VEGF treatment, is poised to become a new direction in wAMD management, potentially offering superior therapeutic options for patients.