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Platelets are traditionally recognized as critical cells in hemostasis and thrombosis but have also recently been identified to play a significant role in many diseases, including bacterial infections, cancer, and allergic asthma. Platelets store and release important messenger molecules via exocytosis from two populations of granules (α- granules with adhesive protein species and δ- granules with small molecule/ion species). However, very little known about how chemical messengers are stored in these granules and the driving forces for secretion into the blood stream, thus limiting the development of new therapeutic approaches to manage the role of platelets in many physiological events. Carbon-fiber microelectrode amperometry (CFMA) enables both quantal and kinetic analysis of the exocytotic event of single cell with sub-ms time resolution but is limited to measuring electroactive species from δ-granules. Localized surface plasmon resonance (LSPR) spectroscopy is a complementary tool that offers an outstanding sensing ability by measuring the extremely small changes in the sensing media. This work aims to overcome the gap in fundamental knowledge about platelet granular storage and secretion by detecting serotonin secretion from δ- granules using CFMA and Platelet factor 4 (PF4) secretion from α- granules using LSPR. These measurements are performed while exposing platelets to different stimulants, including ionomycin, adenosine diphosphate (ADP), and thrombin. Significant differences are seen in both α- and δ-granule secretion with varied stimulant exposure, and these combined measurements yield biophysical insight into the mechanism behind these secretory behaviors.