Rationale: Diabetic neuropathy is a prevalent and debilitating complication of diabetes, necessitating effective pain management strategies. While pharmacological treatments, including opioids, are commonly employed, they pose significant challenges due to the risk of developing opioid-induced hyperalgesia (OIH). This case report aims to illustrate the efficacy of a comprehensive, multidisciplinary approach in managing painful diabetic neuropathy complicated by OIH. Patient concerns: A 64-year-old male patient presented to the Pain Treatment Clinic with severe lower limb pain due to diabetic polyneuropathy. He had a history of multiple comorbidities. Diagnoses: The patient’s condition and physical examination suggested the presence of opioid-induced hyperalgesia (OIH). Despite the increased dose of opioids, the patient did not report significant constipation or breathing difficulties but experienced drowsiness and dry mouth. A diagnosis of opioid and benzodiazepine dependence was made. Interventions: The treatment plan involved the initiation of pregabalin and duloxetine, gradual reduction of opioid use, and psychiatric support for addiction management. Outcomes: Over 12 months, the patient experienced significant pain reduction and minimal adverse effects. Lessons: Effective management of OIH involves gradual opioid tapering and a multimodal therapeutic approach. However, the optimal treatment strategies and the frequency of OIH occurrence remain areas of uncertainty, relying heavily on clinical expertise and individualized patient care. Further research is needed to refine these treatment strategies and improve patient outcomes.