Multiple sclerosis (MS), an autoimmune disorder associated with spinal cord and brain, chiefly affects white matter. Regarding the complexity as well as heterogenic etiology of this disease, the treatment of MS has been a challenging issue up to now. Researchers are working to develop new therapeutic strategies and drugs as complementary therapies. MS diagnosis significantly depends on the findings of Magnetic resonance imaging (MRI) examination. In this imaging technique, gadolinium is used as a contrast agent to reveal active plaques intending to destroy the blood-brain barrier. It also detects plaques which are not correlated with neurological symptoms. It has been attempted to determine biomarkers related to different dimensions of MS in various organizational hierarchy levels of the human anatomy (i.e., cells, proteins, RNA, and DNA). These biomarkers are able to be appropriate diagnostic tools for MS diagnosis. In this review, we summarized the application of MRI and biochemical biomarkers to monitor MS patients. Moreover, we highlighted the joint application of MRI and biomarkers for the diagnosis of MS subjects.