Introduction: Acorus calamus Linn. from the Acoraceae family exhibits several benefits in neurological disorders but has not been studied for chronic constriction injury (CCI) of median nerve induced neuropathic pain. Damage to median nerve leads to work-related musculoskeletal disorders (WMSDs). this study aimed to assess the effects of the ethanolic root extract of Acorus calamus (EAC) on CCI-induced neuropathic pain and WMSDs in rats. Methods: Animals were randomly divided into 7 groups of 8 animals each. Group 1. Normal control, 2. Sham control, 3. CCI, 4. CCI+ vehicle (CMC), 5. CCI+gabapentin (50 mg/kg), 6. CCI+EAC (20 mg/kg), 7. CCI+EAC (40 mg/kg). On day 0, rats were subjected to the surgical procedure of exposure and ligation of the median nerve-produced CCI at the forearm level. Pain-sensitive tests (i.e., hot plate test, Randall Selitto test), and functional analysis (i.e., walking track) were performed. Total protein, lipid peroxidation, and histopathological changes were also estimated. Results: CCI significantly increased thermal and mechanical hyperalgesia, raised median functional index (walking track analysis), and induced biochemical and histological disruptions. Oral administration of EAC (40 mg/kg) and gabapentin (50 mg/kg) notably lowered CCI-induced nociceptive pain threshold, improved median nerve functional index, and mitigated tissue histological alterations. Conclusion: EAC has been found to decrease CCI-induced neuropathic pain of the median nerve. Its mechanisms likely involve neuroprotective, antioxidant, and anti-inflammatory properties.