Objectives To investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for >= 10 years. Design A retrospective study. Participants Patients aged >= 50 with a diagnosis of T2DM no less than 10 years were included. Methods Variables predisposing to AMD were reviewed; the potential confounders related to T2DM or AMD were selected from literature records; AMD and diabetic retinopathy (DR) were diagnosed by funduscopy, optical coherence tomography and/or fluorescein angiography. The subgroup analysis was performed in early and late AMD. The protective effect of metformin was evaluated in duration-response and dose-response patterns. Results A total of 324 patients (115 metformin non-users and 209 users) were included in the final analysis. AMD was observed in 15.8% of metformin users and 45.2% of metformin non-users (p<0.0001). The ORs for any AMD, early AMD and late AMD present in patients with DR were 0.06 (0.02-0.20), 0.03 (0.00-0.20) and 0.17 (0.04-0.75). The serum high-density lipoprotein level was positively associated with the late AMD risk (p=0.0054). When analysed by the tertiles of cumulative duration, a similarly reduced risk was observed for the second (5-9 years) (OR: 0.24, 95% CI: 0.08 to 0.75) and third tertiles (>= 10 years) (OR: 0.22, 95% CI: 0.09 to 0.52) compared with the first tertile (<= 4 years). Conclusion Among patients with T2DM for >= 10 years, metformin users were less likely to develop any AMD and early AMD than non-users; however, the late AMD was not significantly associated with the use of metformin. Also, AMD was less prevalent in patients with DR. The prolonged metformin treatment with a high cumulative dose enhanced the protective effect against AMD. Metformin significantly reduces the AMD risk when the cumulative duration is >5 years.