Background: No previous studies have assessed the psychometric properties of the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in the Persian language of Iran. This study was designed and conducted to evaluate the validity and reliability of the Persian version using a sample of persons with multiple sclerosis in Ahvaz, Iran. Methods: The methodological study was conducted in two stages: First, the 36 items of the original WHODAS 2.0 were translated to create a Persian version, after which the translation validity and psychometric properties were tested. The factor structure of the instrument was also tested using exploratory and confirmatory factor analyses. Results: The intraclass correlation coefficients were very good to excellent, varying between 0.82 and 0.99 for the six domains, and all domains had Cronbach’s α reliability values of above 0.70. For construct validity, results showed negative and strong correlation between the total score of WHODAS 2.0 and the Multiple Sclerosis Quality of Life-54. Exploratory factor analysis divided the Persian version of WHODAS 2.0 into seven factors for multiple sclerosis patients. Conclusion The results of this study indicate that the Persian version of WHODAS 2.0 is a valid and reliable instrument to study the disabilities of people with multiple sclerosis.