Brain-Derived Neurotrophic Factor (BDNF) serves as a modulator for neurotransmitters by participating in neuronal plasticity, essential for their growth and neuronal survival. It also shows a wide range of expression patterns in the systemic and peripheral tissues; thereby, its biological actions are not just limited to the CNS but may a vital role in peripheral disorders, such as Diabetes Mellitus (DM). Platelets serve as one of the major sources of BDNF, which regulates energy homeostasis and glucose metabolism by participating in the expression of specific pro-survival genes. It also prevents β cell exhaustion, thus may prove to be a key factor for the management of DM. The current article reviews the intricate role of BDNF in Type 2 DM (T2DM) by involving platelet reactivity and its association with these selected inflammatory platelet activator mediators. Besides, certain adipocytokines, such as adiponectin and leptin, are also involved in the metabolism of glucose during diabetes, which has been clearly proven by recent experimental studies and thus relating BDNF with adipocytokines. It is also involved in the modulation of secretion of various neurotransmitters, peptides and hormones like gherin, leptin and insulin, suggesting its association with T2DM. Thus, based on various evidence, BDNF can be categorised as a potential biomarker in predicting the development of T2DM and may have a distinctive role in the management of this disorder.