Background/Objectives: Ischemic stroke is a leading cause of disability and mortality worldwide, with current therapies limited in addressing its complex pathophysiological mechanisms, such as inflammation, oxidative stress, apoptosis, and impaired autophagy. Glycyrrhizic acid (GA), a bioactive compound from licorice (Glycyrrhiza glabra L.), has demonstrated neuroprotective properties in preclinical studies. This review consolidates current evidence on GA’s pharmacological mechanisms and assesses its potential as a therapeutic agent for ischemic stroke. Methods: This review examines findings from recent preclinical studies and reviews on GA’s neuroprotective effects, focusing on its modulation of inflammation, oxidative stress, apoptosis, and autophagy. Studies were identified from major scientific databases, including PubMed, Web of Science, and Embase, covering research from January 2000 to August 2024. Results: GA has demonstrated significant neuroprotective effects through the modulation of key pathways, including HMGB1/TLR4/NF-κB and Keap1/Nrf2, thereby reducing neuroinflammation, oxidative stress, and apoptosis. Additionally, GA promotes autophagy and modulates immune responses, suggesting it could serve as an adjunct therapy to enhance the efficacy and safety of existing treatments, such as thrombolysis. Conclusions: Current findings underscore GA’s potential as a multi-targeted neuroprotective agent in ischemic stroke, highlighting its anti-inflammatory, antioxidant, and anti-apoptotic properties. However, while preclinical data are promising, further clinical trials are necessary to validate GA’s therapeutic potential in humans. This review provides a comprehensive overview of GA’s mechanisms of action, proposing directions for future research to explore its role in ischemic stroke management.

Ischemic stroke induces complex neuroinflammatory cascades, where microglial autophagy and mitophagy serve dual roles in both injury amplification and tissue repair. This scoping review synthesized current evidence on their regulatory mechanisms and therapeutic implications. Literature was identified via PubMed and Embase, yielding 79 records, from which 39 original research articles and 13 review papers were included after eligibility screening. Search terms included “microglia,” “autophagy,” and “ischemic stroke.” Protective autophagy was frequently associated with AMPK activation, mTOR inhibition, and mitophagy pathways such as PINK1/Parkin and BNIP3/NIX, facilitating mitochondrial clearance, M2 polarization, and anti-inflammatory signaling. Therapeutic agents such as rapamycin, Tat-Beclin 1, and Urolithin A consistently demonstrated neuroprotection in preclinical stroke models. In contrast, excessive or prolonged autophagic activation was linked to inflammasome amplification, oxidative stress, and phagoptosis. Limited human studies reported associations between elevated serum ATG5 levels or ATG7 polymorphisms and worse clinical outcomes, suggesting preliminary translational relevance. These findings support the potential of phase-specific modulation of microglial autophagy as a therapeutic avenue for stroke, although further validation in human models and development of autophagy biomarkers are needed for clinical application.