The endoscopic transorbital approach (ETOA) has emerged as a promising minimally invasive technique for resection of lesions in the mediobasal temporal region (MTR) due to its potential to preserve the integrity of the optic radiation (OR). This study evaluated the safety and efficacy of ETOA using an OR-sparing surgical strategy for mediobasal temporal lesions. A retrospective review was conducted of the medical records of 15 patients (7 females and 8 males) who underwent ETOA for lesions in the MTR between November 2017 and November 2022. Preoperative diffusion tensor imaging (DTI) tractography of the OR was utilized in all cases for surgical planning to visualize the spatial relations between the OR and the target mediobasal temporal lesion. The median age of the treated patients was 43 years (range 22-76 years), with a median follow-up duration of 12 months (range 6-35 months). Eleven lesions (73.3%) involved only the anterior segment of the MTR, while 4 lesions (26.7%) affected both the anterior and middle segments. Gross-total resection was achieved in 13 patients (86.7%) and subtotal resection in 2 (13.3%). The final pathologies included low-grade glioma (n = 5), cavernous malformation (n = 3), glioblastoma multiforme (n = 2), multinodular and vacuolating neuronal tumor (n = 1), pleomorphic xanthoastrocytoma (n = 1), anaplastic oligodendroglioma (n = 1), adenoid cystic carcinoma (n = 1), and metastatic renal cell carcinoma (n = 1). Postoperative neuro-ophthalmological examinations revealed that all patients maintained their previous visual function. Follow-up DTI tractography further confirmed the preservation of the preoperative ORs in the treated patients. No postoperative CSF leaks, infections, or cosmetic problems occurred in this series. The combined use of ETOA and OR tractography appears to be a feasible approach for resecting lesions involving the MTR, especially in the anterior segment. In the authors' experience, this surgical strategy enables maximal safe resection while minimizing the risk of postoperative visual dysfunction. Further studies with larger sample sizes are warranted to validate these findings and assess long-term outcomes.