Magnetic resonance spectroscopy (MRS) provides non-invasive information about metabolic features in different regions of the brain affected by mesial temporal sclerosis (MTS). To review articles analyzing the most common alterations in biochemical parameters in MTS and the applications of MRS in presurgical assessment. We undertook a systematic literature search for MRS in MTS in PubMed, SCOPUS, and Cochrane based on the MESH terms ""Magnetic Resonance Spectroscopy", "Proton Magnetic Resonance Spectroscopy", "Carbon-13 Magnetic Resonance Spectroscopy", "1H-MRS", "31P-MRS", "mesial temporal sclerosis", "hippocampal sclerosis", "mesial temporal seizure", and "mesial temporal epilepsy". Of the initial 134 articles found, 30 were selected after the exclusion process. Of these, 13 detected a decrease in N-acetylaspartate (NAA), 9 showed a decreased in the ratio NAA/Cho+Cr, and 8 demonstrated a decreased in the ratio NAA/Cr, all of them in the ipsilateral hippocampus. Nine studies also found reduced NAA levels in extrahippocampal regions. The main findings were a decrease in NAA in the ipsilateral hippocampus. In addition, NAA levels were low outside the hippocampus so MTS could be a more extensive disease. Patients without MTS also presented a decrease in NAA in the ipsilateral hippocampus although NAA was even lower in the MTS patients. Thus, MRS could be useful in the presurgical evaluation to locate the epileptogenic focus, but not specific for the diagnosis of MTS.