Background: Acute ischemic stroke (AIS) remains among the leading causes of mortality and functional disability worldwide. The consolidation of mechanical thrombectomy as the standard of care for large vessel occlusions has revolutionized disease management, increasing cerebral reperfusion rates and improving clinical outcomes. However, the persistence of neurological deficits in a subset of reperfused patients highlights the need for complementary strategies focused on neuroprotection and multidisciplinary rehabilitation. In this context, structured in-hospital protocols play a fundamental role in integrating reperfusion therapies, neuroprotective measures, and functional recovery.  Objective: To analyze the scientific evidence related to neuroprotective strategies applied to acute ischemic stroke, emphasizing their association with mechanical thrombectomy and their integration into in-hospital care and multidisciplinary rehabilitation protocols.  Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane Library, SciELO, and the Virtual Health Library (VHL) databases, including studies published between 2013 and 2026. Clinical trials, observational studies, systematic reviews, meta-analyses, and clinical guidelines related to mechanical thrombectomy, cerebral neuroprotection, in-hospital stroke protocols, and multidisciplinary rehabilitation were selected. After applying eligibility criteria, 75 studies were included in the qualitative synthesis.  Results: The studies demonstrated that mechanical thrombectomy constitutes the primary reperfusion strategy for patients with large vessel occlusion, presenting a significant impact on reducing functional disability. Neuroprotective measures, including the management of blood pressure, blood glucose, body temperature, and oxygenation, proved fundamental in minimizing secondary brain injury and enhancing the benefits of reperfusion. Furthermore, care in Stroke Units and the integrated practice of physicians, nurses, and physical therapists contributed to the reduction of in-hospital complications, improvement of neurological outcomes, and increased functional independence. Early mobilization, respiratory management, and structured rehabilitation programs were highlighted as essential components of post-stroke recovery.  Conclusions: The association between mechanical thrombectomy, neuroprotective strategies, and multidisciplinary rehabilitation forms the basis of modern in-hospital protocols for acute ischemic stroke. The integration of these interventions promotes the preservation of the ischemic penumbra, reduces complications, and improves functional outcomes. The strengthening of Stroke Units and the development of novel neuroprotective approaches represent promising perspectives for optimizing the care of patients affected by this condition.