Objective To investigate the clinical value of diffusion tensor imaging (DTI) in preoperative epileptogenic focus localization, surgical planning, and postoperative cerebral white matter microstructural assessment in patients with drug-resistant epilepsy (DRE). Methods A retrospective analysis was conducted on the clinical data of 80 patients with DRE who underwent surgical treatment in the Department of Neurosurgery, Anhui Provincial Hospital, from January 2022 to December 2024. Based on the preoperative evaluation method, patients were divided into the DTI-guided group (n＝40) and the conventional imaging group (n＝40). In addition to conventional magnetic resonance imaging (MRI) and video electroencephalography (VEEG), the DTI-guided group integrated DTI parameters and fiber tractography results to individualize the planning of the minimal safe resection margin. The conventional imaging group formulated the surgical plan solely based on conventional MRI and VEEG findings. All patients were followed up for 12 months. Engel classification was used to evaluate surgical outcomes. Fractional anisotropy (FA), mean diffusivity (MD), and apparent diffusion coefficient (ADC) values were compared between and within groups. Spearman rank correlation analysis was performed to assess the relationship between FA recovery and seizure control. Results The 12-month favorable outcome rate in the DTI-guided group was 95.0% (38/40), significantly higher than the 80.0% (32/40) in the conventional imaging group (χ2＝4.111, P＝0.043). One week after the DTI-guided group surgery, the FA value significantly increased compared to the preoperative value, while the MD and ADC values significantly decreased (all P＜0.001), and the improvement persisted until 12 months after the surgery. There were no statistically significant differences in the changes of each parameter in the conventional imaging group (all P＞0.05). At 12 months after the surgery, there were statistically significant differences in the FA, MD, and ADC values between the two groups (all P＜0.01). The localization accuracy of the epileptogenic focus was 92.5% (37/40) in the DTI-guided group, significantly higher than 75.0% (30/40) in the conventional imaging group (χ2＝4.501, P＝0.034). The overall complication rate was 7.5% (3/40) in the DTI-guided group, with no permanent neurological deficits, compared with 15.0% (6/40, including one case of permanent memory impairment) in the conventional imaging group, though the difference was not statistically significant (P＝0.288). Spearman correlation analysis revealed a significant positive correlation between FA recovery at 12 months and Engel class in the DTI-guided group (rs＝0.62, P＜0.01). Conclusion DTI can precisely locate the epileptogenic focus, optimize the extent of surgical resection, significantly improve surgical outcomes, and effectively protect neurological function. The dynamic evolution of postoperative FA, MD, and ADC parameters can objectively reflect cerebral white matter fiber tract remodeling and hold value for monitoring and predicting epilepsy prognosis.