Background: Major Depressive Disorder is a global health issue that affects more than 300 million people worldwide, which is about 4.4% of the global population. Treatment usually consists of a combination of antidepressant medication and therapy. However, approximately 30% of individuals with Major Depressive Disorder experience a Treatment-Resistant Depression (a failure to respond to at least two antidepressants used in a regular dosage and time interval). Our research aims to investigate how effective Mindfulness-Based Cognitive Therapy is for individuals with Treatment-Resistant Depression. Materials and Methods: We will conduct a thorough search for publications in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Additionally, we will manually review the reference lists of the included studies to find any other potentially relevant studies. There will be no restrictions on language or publication date. The quality of the included studies will be assessed independently using the Jadad scale (Oxford quality scoring system). To assess the certainty of the evidence, we will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression. Ethics and dissemination:  Ethical approval is not necessary because individual patient data is not being collected. Our objective is to publish the systematic review in an open-access medical journal once the review process is completed. Prospero registration ID: CRD42023411978. Registered on April 07, 2023.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Not Applicable

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study does not require ethical approval because it involves a systematic review and meta-analysis of previously published studies. No individual patient data is being collected or analyzed. Therefore, no Institutional Review Board (IRB) or oversight body approval is necessary for this research. Details of the IRB/Oversight Body: Not applicable.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Not Applicable

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Not Applicable

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Not Applicable

No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion.