Multiple Sclerosis (MS) is a chronic demyelination disease of the central nervous system (CNS). The gut-brain axis involves communication between the nervous, endocrine, and immune systems. Probiotics can positively impact immune and inflammatory responses by regulating gut microbiota. A total of 40 MS patients (average age of 34.38 ± 6.65) were examined to determine the effect of the Saccharomyces boulardii supplement for four months compared to a placebo. The results showed that the Saccharomyces boulardii significantly decreased the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) compared to the placebo (P < 0.001). The serum antioxidant capacity (TAC) also increased significantly in the probiotic group compared to the placebo (p = 0.004). Both the probiotic and placebo groups showed a reduction in the oxidative stress indicator malondialdehyde (MDA), but there was no significant difference between the two groups. Pain intensity (measured by Visual Analogue Scale) and fatigue severity (measured by Fatigue Severity Scale) significantly decreased in the probiotic group compared to the placebo (p = 0.004 and p = 0.01, respectively). The probiotic group experienced significant improvement in some quality of life scales (measured by 36-Item Short Form Survey) and somatic and social dysfunction subscale of General Health Questionnaire scores compared to the placebo group (p = 0.01). The study suggests that the Saccharomyces boulardii probiotic supplement may benefit inflammatory markers, oxidative stress indicators, pain, fatigue, and quality of life in MS patients.