<p>Ischemic stroke remains a leading cause of death and long-term disability, driven by oxidative stress, inflammation, and cellular energy failure. Among the adaptive mechanisms activated during ischemia, autophagy a lysosomal degradation process plays a paradoxical role in determining neuronal fate. This review provides a comprehensive analysis of autophagy’s temporal and context-dependent functions in ischemic stroke. Autophagy is initially activated as a neuroprotective response to clear damaged organelles and misfolded proteins, thereby maintaining mitochondrial integrity and reducing oxidative stress through the regulation of AMPK, mTOR, and SIRT1 signaling pathways. However, when excessively sustained, autophagy becomes maladaptive, promoting neuronal apoptosis, blood–brain barrier disruption, and neuroinflammation. Selective autophagy forms including mitophagy, lipophagy, ribophagy, pexophagy, and aggrephagy further modulate ischemic outcomes by targeting specific subcellular components for degradation. Experimental evidence demonstrates that controlled activation of autophagy alleviates ischemic injury, while overactivation leads to cellular demise. Pharmacologic modulators such as rapamycin, resveratrol, metformin, and propofol have shown potential in restoring autophagic balance and reducing infarct size in preclinical models. Collectively, autophagy functions as a double-edged sword in ischemic stroke, where its beneficial or detrimental effects depend on timing, duration, and intensity of activation. Understanding the molecular switches governing this balance could enable the design of targeted autophagy modulators to optimize neuroprotection and recovery in ischemic stroke.</p>