Platelets are anucleate blood cells traditionally associated with hemostasis but now increasingly recognized for their multifaceted roles in immunity, inflammation, and tissue repair. Advances in platelet proteomics, employing high-throughput techniques such as mass spectrometry, have significantly enhanced our understanding of platelet biology and its clinical implications in transfusion medicine. Platelet proteomics offers a retrospective view of physiological and pathological changes over the platelet’s 7–10-day lifespan, making it a unique tool for studying cumulative biological events. Recent applications include the identification of biomarkers for cardiovascular, infectious, autoimmune diseases and cancer. In neurodegeneration and aging, platelets have been explored for their shared molecular pathways with neurons, with findings implicating Tau, amyloid-beta, and alpha-synuclein as potential biomarkers. Proteomics is also emerging as an important factor in the development of evidence-based, tailor-made platelet-derived therapies. While promising, platelet proteomics requires further standardization and computational advances to support transitioning from research to routine clinical practice.