This systematic review evaluates the effectiveness of various neuroprotective strategies in enhancing recovery following acute ischemic stroke, focusing on interventions such as normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin. Drawing upon data from six primary studies, including randomized controlled trials (RCTs) and meta-analyses, we assessed these therapies' impact on functional outcomes, motor recovery, and neurological improvement. Normobaric oxygen, across 12 RCTs, demonstrated limited efficacy in improving recovery outcomes or reducing mortality. Lithium, supported by animal models but with inconclusive human data, showed potential in reducing stroke volume but did not significantly enhance functional recovery in clinical trials. SSRIs, particularly fluoxetine, showed moderate success in improving motor recovery, as evidenced by the FLAME (Fluoxetine for Motor Recovery after Acute Ischaemic Stroke) trial and meta-analyses. Cerebrolysin demonstrated consistent improvement in early neurological function and motor recovery, with a number-needed-to-treat (NNT) of 7.1 for early NIHSS (National Institutes of Health Stroke Scale) score improvements. Our Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search covered PubMed, Medline, Embase, and the Cochrane Library up to September 2024. These findings emphasize the mixed efficacy of these neuroprotective interventions and underscore the necessity for personalized treatment protocols and further large-scale, controlled trials to clarify their roles in clinical practice. This review contributes to the ongoing dialogue on optimizing post-stroke recovery and highlights the critical need for evidence-based neuroprotective strategies.