Fingolimod is an immunotherapeutic drug approved in certain countries as first-line therapy for relapsing-remitting multiple sclerosis (RRMS). The drug has been shown to alter the expression of several coding and non-coding genes. In the current study, we assessed the expression of miR-506-3p, miR-217, miR-381-3p, miR-1827, miR-449a and miR-655-3p in peripheral blood of patients with RRMS undergoing treatment with fingolimod compared with healthy controls. We also compared the expression of these miRNAs between fingolimod responders and non-responders to determine their relevance with regard to response to fingolimod. Expression of miR-381-3p was significantly higher in responders than in controls (RE difference = 3.903, P = 0.005), while expression of miR-655-3p was significantly lower in both responders and non-responders compared with controls (RE difference = -1.03, P = 0.014; RE difference = -1.41, P < 0.0001, respectively). No difference was found in the expression of other miRNAs between study subgroups. In addition, there was no significant difference in the expression of any miRNA between responders and non-responders. Although there were significant pairwise correlations between expression levels of all of the assessed miRNAs in controls, MS patients exhibited differences in correlation patterns. Expression of miR-381-3p was correlated with age in responders. However, expression of other miRNAs did not correlate with age in any study subgroup. The current study indicates a possible role for miR-655-3p and miR-381-3p in the pathogenesis of MS or possible effects of fingolimod on the expression of these miRNAs. Future studies are needed to verify these results in larger patient populations.