Peripheral nerve injuries affect 13–23 out of 100,000 people annually, with Wallerian degeneration and subsequent inflammatory/oxidative responses critically impacting recovery. Aloperine, a natural alkaloid from Sophora alopecuroides L., exhibits potent anti-inflammatory and antioxidant properties but has never been studied for nerve repair. In this study, we aimed to investigate whether aloperine could enhance peripheral nerve regeneration by modulating inflammation and oxidative stress in a rat sciatic nerve injury model. Thirty male Wistar rats underwent sciatic nerve neurotmesis with epineural repair. Animals were divided into surgical controls (Group A), aloperine-treated rats (Group B; single 100 mg/kg intraperitoneal dose), and intact controls (Group C). After 8 weeks, outcomes were assessed via functional tests (pinprick, hot plate, extensor postural thrust), biochemical analyses (TNF-α, IL-6, IL-10, TOS/TAS), and histomorphometric evaluations (axon counts, diameter indices, immunohistochemistry). Aloperine treatment significantly improved functional recovery, with near-normal hot plate latency and motor performance. Biochemically, it reduced pro-inflammatory markers (TNF-α) while elevating IL-10. Oxidative stress was attenuated. Histologically, treated nerves showed better-preserved axonal architecture (reduced inflammation). This first investigation of aloperine for nerve repair demonstrates its therapeutic potential through dual anti-inflammatory and antioxidant mechanisms, significantly improving functional and structural outcomes. These findings support its development as a novel treatment for peripheral nerve injuries.