Depression is an aversion to activity disorder which could lead to somatic dysfunctions such as insomnia, excessive sleeping, body aches, listlessness, and irritable bowel syndrome. The World Health Organization has projected the depression to be the second leading cause of disability worldwide by 2020. The physical and mental ill effects of somatic depression can be addressed using the osteopathic manipulative treatment. Therefore, the purpose of the present case report is to explore the effect of myofascial release (MFR) technique and myofascial unwinding (MFU) in the somatic depression. We reported a case of a 39-year-old female diagnosed as dysthymia with moderate depression with somatic symptoms. She was treated with MFR and MFU for 4 weeks. Depression was scored using Hamilton Depression Rating Scale (HDRS), and quality of life was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). Both were administered preintervention and 6 weeks postintervention. The application of MFR and MFU resulted in the improved scores on both HDRS and Q-LES-Q-SF. The present case positive results have proven the effectiveness of MFR and MFU as an important adjunctive treatment strategy.