Here, we performed a comprehensive proteome profiling of platelets collected from 18 healthy subjects before and after administration of sarpogrelate. For each subject, platelets were isolated before and then again after drug administration to investigate the alteration in the platelet proteome by sarpogrelate. A sample preparation method involving filter-aided sample preparation (FASP) was used to improve extraction of proteins including both soluble and membraneous proteins. Moreover, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) coupled with extensive fractionation was used to generate a comprehensive proteome of platelets.