Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by the presence of insulin resistance that leads to hyperglycemia and increased hemoglobin A1c (HbA1c) levels. Here, we review emerging clinical and experimental evidence about exercise-linked irisin consequences to cardiovascular and mental health in T2DM. Irisin is a myokine produced in response to exercise, which has been pointed as a relevant mechanism of action to explain the benefits of exercise on cardiovascular and mental health in T2DM patients. Different types of exercise, from aerobic to resistance training, are effective to improve mental health and cognitive function in T2DM. It is widely known that the regular practice of exercise provides several physiological benefits to subjects with T2DM, such as managing glycemic and blood pressure levels. Lifestyle modifications, including physical exercise training, are necessary to prevent T2DM development and its associated complications. Therefore, atherosclerotic cardiovascular diseases (CVD) and mental health issues have been strongly associated with T2DM. Chronic exposure to a T2DM microenvironment with hyperglycemia, hyperinsulinemia, oxidative stress and increased levels of proinflammatory mediators, has negative consequences to the cardiovascular system and mental health. Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and hyperglycemia.