Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to neurological disability, more pronounced in the progressive phase. Teriflunomide, an oral disease-modifying therapy, has shown potential neuroprotective effects beyond relapse reduction, including preservation of brain integrity and mitigation of disability progression. This review provides supportive evidence of the effects of teriflunomide on disability progression, cognition, and MRI markers of neurodegeneration in MS. Methods PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched to identify relevant studies evaluating the effects of teriflunomide on disability progression, cognition, and MRI markers of neurodegeneration in MS such as brain volume loss. Clinical trials, extension studies, comparator studies, and real-world observational cohorts were reviewed. Discussion Teriflunomide demonstrated consistent effects stabilizing disability progression, maintaining cognitive performance, reducing brain volume loss and preserving gray and white matter integrity across multiple studies. Findings from various studies support its role in limiting disability progression. Proposed mechanisms include preservation of mitochondrial integrity, reduction of oxidative stress, and promotion of remyelination. Although higher-efficacy therapies may provide superior inflammatory control, teriflunomide may have an important role in the long-term management of MS. Conclusion Teriflunomide is emerging as a valuable, multi-faceted contributor to the MS treatment landscape, with data supporting its role in preserving brain volume, slowing disability progression, and maintaining cognitive function. Additionally, its favorable long-term tolerability and minimal immunocompromise effects further support its value as a therapeutic option over the longer course in PwMS.