Aim: The aim of the present study was to evaluate the effectiveness and safety of combination therapy using metformin and MTX in the treatment of psoriasis patients with metabolic syndrome.Material & Methods:This study was single-blind clinical trial was conducted for the period of 6 months with 100 patient’s diagnosedwith plaque psoriasis who were being treated. Allpatients met full criteria to participate in this research. This study was approved by the Board of Ethical committee.Results:Patients treated with the combined regimen showed measured improvement in disease status compared to those treated with MTX monotherapy. The Psoriasis Area and Severity Index (PASI) scores of psoriasis patients with metabolic syndrome using the metformin and MTX combination were significantly lower than those treated with MTX only (p<0.05). The combination treatment group also showed a significant decrease in blood sugar and triglyceride levels after 3 months (p<0.05). However, there were no significant differences in subclinical indexes between the treatment and control groups.Conclusion:In this treatment sample, a combination of metformin and MTX in psoriasis patients with metabolic syndrome showed positive responses and no serious side effects.