Introduction: Women dependent on drugs face greater challenges in accessing treatment services, and the use of psychological interventions to improve the skills necessary for substance abstinence in women has been overlooked. Objective: This study aimed to investigate the effectiveness of schema therapy on brain-behavioral systems, emotional dysregulation, and abstinence self-efficacy among women. Method: The research employed a semi-experimental design with a pre-test-post-test- follow-up approach with a control group. The statistical population included all women dependent on drugs in Tehran in 2023. A purposive sampling method was used to select 30 participants, who were randomly assigned to either the schema therapy group or the control group. Schema therapy was conducted over 20 sessions based on the protocol by Young et al. (2003) and Young & Kloss (2003). Data were collected using the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale by Carver and White (1994), the Difficulties in Emotion Regulation Scale (DERS) by Gratz and Roemer (2004), and the Drug Abstinence Self-Efficacy Scale (DASES) by Martin (1995). Data analysis was performed using SPSS.v24 software, employing repeated measures ANOVA and Bonferroni post hoc tests. Findings: The results indicated that schema therapy was effective in improving the overall score of the brain-behavioral system and its components of behavioral inhibition and activation, with the results remaining stable at the follow-up stage. Additionally, schema therapy significantly impacted the overall emotional dysregulation score and the components of non-acceptance, goals, awareness, and strategies, with this effectiveness also persisting at follow-up. Furthermore, schema therapy was effective in enhancing the overall abstinence self-efficacy score and the components of problem-solving, decision-making, communication, and self-assertion, with effects continuing to the follow-up stage. Conclusion: Based on the obtained results, the use of schema therapy is recommended as a complementary intervention alongside other therapeutic measures to improve brain-behavioral systems, emotional dysregulation, and abstinence self-efficacy among women dependent on drugs.