Ranolazine is an anti-anginal medication that reduces the sodium-dependent calcium overload via the inhibition of the late sodium current. After its approval for the treatment of chronic angina in 2006 in the USA, ranolazine has been reported to have several pleiotropic effects on various cardiac conditions, such as atrial fibrillation, ventricular arrhythmias, diastolic and microvascular dysfunction, and pulmonary arterial hypertension. Recently, several studies reported some promising results on the potential benefits of ranolazine on glycemic control. Though the mechanism of the antihyperglycemic effect is still unknown, ranolazine may exert the effect through β cell preservation, inhibition of glucose secretion, and enhancement of insulin secretion in a glucose-dependent manner. Given the increased risk of cardiovascular disease in patients with diabetes, it will be useful if one medication can simultaneously improve chronic angina and diabetes. Therefore, ranolazine could be a favored choice among other anti-anginal agents for patients with comorbidity of chronic angina and diabetes mellitus. In this review, we summarize the available data from clinical studies and provide valuable insight into defining the target population for the antihyperglycemic effect of ranolazine.