Ischemic stroke (IS) constitutes a major threat to human health. Vascular recanalization by intravenous thrombolysis and mechanical thrombolysis remain the most significant and effective methods for relief of ischemia. Key elements of these treatments include achieving blood-vessel recanalization, restoring brain-tissue reperfusion, and preserving the ischemic penumbra. However, in achieving the therapeutic goals of vascular recanalization, secondary damage to brain tissue from cerebral ischemia-reperfusion injury (CIRI) must also be addressed. Despite advancements in understanding the pathological processes associated with CIRI, effective interventions to prevent its onset and progression are still lacking. Recent research has indicated that mitophagy and ferroptosis are critical mechanisms in the development of CIRI, and significantly contribute to the onset and progression of IS and CIRI because of common targets and co-occurrence mechanisms. Therefore, exploring and summarizing the potential connections between mitophagy and ferroptosis during CIRI is crucial. In the present review, we mainly focused on the mechanisms of mitochondrial autophagy and ferroptosis, and their interaction, in the development of CIRI. We believe that the data show a strong relationship between mitochondrial autophagy and ferroptosis with interactive regulation. This information may underpin new potential approaches for the prevention and treatment of IS and subsequent CIRI.