Introduction: Mind-body medical interventions are usually used to treat a wide range of mental health conditions and Shirodharais one of the Ultimate mind-bodytreatments in Ayurveda. Although, Ayurvedais one of the worlds oldest holistic healing systems and has a promising potential in the management of Vishada [Major Depressive Disorder (MDD)]. However, systematic and evidence-based research on the subject is still lacking.The aim of this review was to systematically assess andanalyze the effectivenessof Shirodhara therapy in MDD and to explore scientific explanations for its therapeutic utility. Methods: Medline/Pubmed, Google Scholar,ProQuest,and EBSCO were searched through May 2022 and reaped three eligible interventional studies performed on patients with depression, who were administeredShirodhara with or without medicament (modern or herbal preparations). However,there are considerable caveats due to methodological limitations of sample size, design,duration, and the method of administration. These elements have been detailed. Result: Due to the paucity and heterogeneity of the included interventional studies, no meta-analyses were possible to measure the outcomes. Conclusion: Limited evidence supports the use of Shirodhara for depression. However, considering its impact on the psycho-neuro-immunological axis and various bodily systems, Shirodhara shows potential benefits. Further research is needed to evaluate Shirodhara as a standalone or adjunct treatment, including its integration with modern or herbal interventions, in a broader context.