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Abstract Background Treatment-resistance is recognized as a significant dilemma in schizophrenia, which has been reported to involve approximately one-third of patients with schizophrenia. Case presentation This case report described a 12-week treatment course for a 39-year-old Persian man with treatment-refractory schizophrenia, who showed a significant improvement in terms of positive, negative, and cognitive symptoms after taking ursodeoxycholic acid 300 mg capsules twice a day. Also, ursodeoxycholic acid was well tolerated, and he did not exhibit any side effects during treatment, based on interview and physical examination. Conclusion Ursodeoxycholic acid augmentation seems to be an effective treatment strategy for patients with treatment-refractory schizophrenia. However, further investigations in this field need to be carried out through randomized controlled trials.