Vision impairment caused by age-related macular degeneration (AMD) is a global health priority. Retinal pathology is driven by aging and exacerbated by genetic and environmental risk factors. Peripheral blood circulation is increasingly recognised as a contributor to disease initiation and progression, and a source of biomarkers to support earlier diagnosis and personalised treatment strategies. Here we performed an analysis of plasma-derived extracellular vesicle (EV)-enriched samples from 11 AMD and 11 controls. A proteomic analysis identified significantly changed proteins in AMD, many of which appeared downregulated with a strong interaction network including AMD-associated complement proteins and endopeptidase inhibitor activity. Importantly, many of the altered proteins were previously reported AMD biomarker candidates and involved in pathways known to influence AMD: oxidative stress response, immune system functioning and proteolysis dysregulation.