<p>This study aims to evaluate the clinical efficacy of tadalafil combined with epalrestat in the treatment of diabetic neurovascular erectile dysfunction (ED). Eighty patients diagnosed with diabetic neurovascular ED admitted to between January 2022 and October 2024 were randomly allocated into two groups (<i>n</i> = 40 each). The control group received tadalafil monotherapy, while the observation group was additionally treated with epalrestat. Both regimens lasted 12 weeks. Outcomes assessed pre- and post-treatment included International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS), modified Sexual Life Quality Questionnaire (mSLQQ-QoL), penile hemodynamic parameters [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and serum markers of endothelial function [endothelin-1 (ET-1), von Willebrand factor (vWF), and asymmetric dimethylarginine (ADMA)]. Treatment safety was also evaluated. Post-treatment, both groups showed significant improvements in IIEF-5 scores, proportion of EHS grade III-IV, and mSLQQ-QoL scores, with greater changes observed in the combination group (<i>P</i> &lt; 0.05). The combination group also demonstrated higher PSV and RI, and lower EDV, ET-1, vWF, and ADMA levels than the control group (<i>P</i> &lt; 0.05). No drug-related adverse events occurred in either group (<i>P</i> &gt; 0.05). Tadalafil combined with epalrestat therapy for diabetic neurovascular ED can synergistically improve erectile function, erection hardness, sexual life quality, penile hemodynamics, and vascular endothelial function, with good safety and no increased risk of drug-related adverse events.</p>