Objective: Vagus Nerve Stimulation (VNS) offers treatment for drug-resistant epilepsy, but the mechanism underlying its efficacy remains unclear. This study aimed to uncover microstructural features in VNS responders and non-responders using diffusion magnetic resonance imaging (dMRI), diffusion models and machine learning techniques. Methods: Data were collected from 19 patients with drug-resistant epilepsy. Diffusion tensor imaging and other multi-compartment models (NODDI, DIAMOND and Microstructure Fingerprinting) were used to compute microstructural metrics within distinct regions of interest (ROIs) outlined on tractography pathways estimated using FreeSurfer and MRtrix3. We calculated the weighted mean, standard deviation, skewness, and kurtosis of the metrics along the tracts for summarising their distribution.