Multiple sclerosis (MS) manifests as progressive disability stemming from the demyelination of axons within the central nervous system, resulting in neuronal loss and atrophy in the brain and spinal cord. Diagnosis typically entails a thorough assessment of medical history, symptoms, physical examination, and various diagnostic procedures, including magnetic resonance imaging, cerebrospinal fluid analysis, blood tests, and electrophysiology. However, existing biomarkers often fail to reliably correlate with disease progression. Understanding the molecular mechanisms driving disease progression, particularly the transition from relapsing-remitting MS (RRMS), marked by inflammation, to secondary progressive MS (SPMS), characterized by neurodegeneration, remains a formidable challenge for healthcare providers. Despite extensive research efforts, dependable markers indicating disease stage and activity remain elusive. Circulating microRNAs (miRNAs) have emerged as promising candidates for both MS diagnosis and prognosis due to their altered expression patterns across the disease spectrum. Differential expression of miRNA panels between RRMS and SPMS holds the potential to offer valuable insights into disease progression and to inform treatment strategies aimed at halting disability advancement. This review seeks to delve into current research exploring the differences in miRNA panel expression across various phases of MS.