Background/Objectives: In Latin America, yerba mate (YM) is a popular infusion processed from the leaves and stems of Ilex paraguariensis. YM has been shown to have anti-inflammatory properties in several studies, although the effect of YM on multiple sclerosis (MS) remains elusive. The purpose of this study was to examine the effect of YM on the development of MS, by using the experimental autoimmune encephalomyelitis (EAE) mouse model while also evaluating its effect over infiltration of immune cells into the central nervous system (CNS) and regulatory T cell (Treg) function. Methods: YM or vehicle were administrated to mice daily by oral gavage for seven days prior to EAE induction and during the entire course of the disease. EAE score was recorded daily, and immune cell infiltration into the CNS was measured by flow cytometry and immunofluorescence. Results: Our results showed that YM administration decreases EAE symptoms and immune cell infiltration into the CNS, along with reducing demyelination, compared to the vehicle treatment. Moreover, an increase in the Treg population, immune cells capable of generating tolerance and decreased inflammation, was observed in mice receiving YM, together with improved Treg suppressive capabilities after YM treatment in vitro. Conclusions: In summary, we showed that YM promotes an immunosuppressive environment by modulating Treg function, reducing EAE symptoms and immune cell infiltration into the brain, and suggesting that YM consumption could be a good cost-effective treatment for MS.