Diabetes mellitus type 2 (DM2) is a hypercoagulable state with enhanced platelet (PLT) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to the formation of clots with high fibrinolysis resistance. The stages of PLT “activation” have been well characterized microscopically, morphometrically, and nanomechanically using a light microscope, transmission electron microscope (TEM), scanning electron microscope (SEM), and atomic force microscope (AFM). Thrombocytes in an “activated” (procoagulant) state play a central role in two main biological processes: hemostasis and vascular vessel repair. Enhanced PLT reactivity in diabetic patients is considered a “pro-thrombotic” state. PLT hematometric indices are higher in retrospective and prospective studies, such as PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (platelet crit), and the PLTs/Ly ratio. The platelet indices MPV and PDW are higher in people with diabetes who have chronic vascular complications, and are statistically significant. PLT parameters/indices are useful biomarkers in the early diagnosis and prognosis of DM2. Precise studies of PLT activation state during DM2 may be useful for new diabetes (DM2) treatment strategies and effective therapeutic agents. Researchers have observed an association between MPV and medications such as insulin, metformin, and sulfonylureas using the blood glucose concentration attached to hemoglobin (HbA1c values) as markers of glycemic control in patients with diabetes. Computational modeling of PLT activation in DM2 is also a controlling factor for thrombocyte distribution and margination in blood vessels, both of which are associated with micro- and macrovascular disease in DM2. PLT-derived microRNAs (miRNAs) are novel molecular biomarkers for the diagnosis and prognosis of DM2, insulin resistance, and diabetes complications. Anti-platelet agents and natural plant products may also be effective in the prevention and secondary treatment of micro- and macrovascular complications in type 2 diabetes mellitus. To determine new ways of diagnosing, treating, predicting, and managing DM2 and its related vascular complications, we propose monitoring a combination of hematological, hemorheological, and hemostatic parameters (indices), which merit future studies.