Background: Mothers who have children with cerebral palsy experience negative self-criticism and failure to adapt to their children's disability due to psychological inflexibility, which makes them more vulnerable to mental diseases. So, the aim of the study was to examine the effect of a self-compassion based nursing intervention on self-criticism and psychological flexibility among mothers of children with cerebral palsy. Methods: A quasi-experimental research design (a pretest-posttest) with a control group was used. A purposive sample of 80 mothers of children were randomly assigned to one of two groups: the intervention group (N = 40) and a control group (N = 40). The study was conducted at the Al Basma Association for Disabled Children, Shebin al-Kom, Menoufia Governorate, Egypt. Four tools were used: (1) a structured interview questionnaire; (2) the self-compassion scale; (3) the forms of self-criticizing and self-reassuring scale; and (4) the acceptance and action questionnaire (AAQ-2). Results: After application of self-compassion based intervention and follow up sessions, the total score of psychological flexibility level in the intervention group significantly improved compared to the control group, while the total mean score of self-criticism subscales (inadequate self, hated self) was significantly reduced among the intervention group compared to a control group. Conclusion: The self-compassion based nursing intervention was an effective intervention for reducing self-criticism and enhancing the level of psychological flexibility among mothers of children with cerebral palsy. Recommendations: Nurses and counselors in physiotherapy and pediatrics departments must undergo comprehensive training in self-compassion to effectively support mothers of children with special need e.g. learning disabilities while they care for their children.