Background Stroke ranks as the fifth leading cause of death in the United States and is the primary contributor to neurological impairments and cognitive deficits, responsible for 5.2% of global deaths. Approximately half of stroke survivors suffer from long-term disabilities, making it a leading cause of disability worldwide. Currently approved treatments for ischemic stroke focus on restoring cerebral blood flow through intravenous thrombolysis and mechanical thrombectomy. Minocycline, a lipophilic protease inhibitor capable of crossing the blood-brain barrier, exhibits anti-inflammatory, antioxidant, and antiapoptotic properties both centrally and peripherally. This literature review aims to assess the efficacy and safety of Minocycline as an adjunctive therapy in treating ischemic stroke and improving post-stroke functional outcomes. Methods We searched PubMed, Google Scholar, and clinicaltrials.gov databases. We used a combination of keywords: acute ischemic stroke, Minocycline, neuroprotection, and neuroinflammation. We included full-text peer-reviewed scholarly articles published within the last decade, randomized controlled trials, and systematic reviews with meta-analyses. We excluded articles in languages other than English, experimental studies and animal studies. Results We systematically reviewed nine articles that met our predefined eligibility criteria and involved 1,010 participants. These studies assessed the effectiveness and safety of Minocycline by comparing groups treated with Minocycline to control groups using the National Institute of Health Stroke Scale. Across the nine studies, there was consistent evidence of substantial clinical improvement among patients treated with Minocycline. However, two of the studies indicated that although Minocycline was deemed safe, it did not result in improved outcomes for patients with acute stroke. Conclusion Minocycline shows promise in mitigating both immediate and prolonged effects of ischemic stroke, demonstrating efficacy with minimal adverse effects even at high dosages. Nonetheless, conflicting results in two studies suggest that small sample sizes might contribute to varying conclusions. Despite the scarcity of data from clinical trials, Minocycline could serve as a valuable adjunctive therapy, particularly for patients in remote areas lacking access to specialized stroke care or those unsuitable for intravenous thrombolysis. Additional randomized clinical studies on a large scale are needed to verify the Minocycline's neuroprotective effects and its potential to improve outcomes and reduce long-term disabilities in ischemic stroke patients.