Introduction: Patients with epilepsy face a variety of physical and psychological tensions that reduce their quality of life. Considering the relationship between cognitive emotion regulation and social self-efficacy with diseases of the central nervous system, one of the methods that can help rehabilitate patients with epilepsy is schema therapy. The present study aimed to determine the effectiveness of schema therapy on cognitive emotion regulation and social self-efficacy in adolescents with epilepsy. Materials and Methods: This investigation was a semi-experimental study with a pre-test/post-test and a control group. The sample consisted of 30 adolescents with epilepsy in Rasht, Iran in the year 2021 selected by the convenience sampling method and randomly assigned into two experimental and control groups (each group 15 individuals). The Cognitive Emotion Regulation Questionnaire and Social Self-Efficacy Scale were used to collect data before and after the treatment. The 10-session schema therapy was performed for the experimental group, but the control group did not receive any treatment. Results: The analysis of covariance results showed that schema therapy improved cognitive emotion regulation and social self-efficacy in adolescents with epilepsy. Conclusion: Schema therapy can be a suitable treatment method to improve emotion regulation and social skills in adolescents with epilepsy and can be beneficial in increasing the life satisfaction of these patients.