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Introduction: The existence of a mentally retarded child in a family leaves negative and irreversible effects on parents, particularly mothers. The purpose of the study was to examine the effectiveness of schema therapy on distress tolerance and resilience of mothers with mentally retarded students. Materials and Methods: In this research, 30 mothers of mentally retarded students, studying in exceptional students in districts 1 and 2 of Zahedan, Iran in 2020, were chosen using the convenient sampling. Then, they were assigned randomly to two control and experimental (schema therapy-based) groups. In the next step, all participants filled out Distress Tolerance Questionnaire and CD Resilience Scale (Connor-Davidson), and the experimental group received eight 2-hour sessions of schema therapy-based training. The Control group received no intervention during the study. The collected data were analyzed through SPSS22 software by using descriptive indicators, univariate and multivariate ANCOVA. Results: The results showed the significant effect (P<0.05) of schema therapy on distress tolerance and resilience so that this therapy could expand distress tolerance and resilience of mothers. Conclusion: According to the obtained results, schema therapy can be recommended as an efficient method to increase distress tolerance and resilience in mothers who have mentally retarded students. [ABSTRACT FROM AUTHOR]