Complex regional pain syndrome (CRPS) is a debilitating condition that typically affects one limb, often triggered by acute trauma. Symptoms include persistent pain, skin sensitivity, swelling, and mobility issues. While various therapeutic approaches exist, evidence for the effectiveness of multimodal treatments is limited. A 25-year-old female presented with CRPS following a sciatic nerve injury due to an intramuscular injection. She experienced severe pain, swelling, and limited mobility in her left ankle. Physical therapy assessment revealed significant weakness and limitations in both active and passive range of motion due to pain and swelling. The patient underwent a holistic treatment consisting of osteopathy and rehabilitation exercises over 36 sessions spanning 9 months. Significant improvements were observed after treatment, including reduced pain, increased mobility, and improved nerve conduction. These findings suggest that a multimodal therapeutic approach may be beneficial in managing CRPS and improving patients’ quality of life.