The incidence and the mortality of ischemic stroke mostly peak in the early morning. This phenomenon suggests that circadian rhythm disorder is closely related to acute ischemic stroke. Although some studies believe that the rise of blood pressure (the so-called morning peak), the increase of platelet aggregation, and the passivation of endothelial function are related to the occurrence of early morning ischemic stroke, its molecular mechanism is largely unknown. Recent studies have found that deacetylase silent information regulator 1 (SIRT1) is involved in regulating clock gene transcription. Moreover, SIRT1 plays an important role in the occurrence, development and treatment of ischemic stroke by deacetylation to inhibit oxidative stress, inflammatory response, autophagy, and apoptosis. Therefore, it is necessary to explore the complex association between circadian rhythm and SIRT1 and their interaction in regulating neuroprotection against ischemic stroke.