Objective: The purpose of this study was to evaluate the gray matter (GM) alterations in patients with mesial temporal lobe epilepsy (MTLE) based on statistical models. Methods: High-resolution MRI data were collected from 64 adult MTLE patients and 100 healthy participants. Voxel Based Morphometry (VBM) and Surfaced Based Morphometry (SBM) analysis were used to detect the alterations of cerebral GM of MTLE. We also built general linear models (GLM) for quantitatively evaluating regions of interest (ROIs) from the corrected VBM, SBM analysis. Results: The corrected VBM and SBM analyses identified discriminable GM alterations in the left and right MTLE groups located in the ipsilateral hippocampus, the perisylvian cortex in the left MTLE group and the bilateral orbitofrontal cortex in the right MTLE group. We extracted the ipsilateral hippocampal volume GLM of both unilateral MTLE groups. History of febrile convulsions and an increased number of AEDs were recognized as risk factors for ipsilateral hippocampus atrophy of unilateral MTLE. Moreover, early onset age was also considered a risk factor for left hippocampus atrophy in left MTLE. Significance: The current study established a quantitative assessment of unilateral MTLE based solely on GM alterations, without any influence of demographic risk factors. By using this GM-based protocol, we found that regions both inside and outside of the temporal lobes may be associated with the epileptic network of MTLE.