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Background Oral submucous fibrosis is characterized by stiffness of oral mucosa, blanching and functional limitation, and areca nut predisposition is considered to be one of the main etiological factors. In recent years, there is an increasing prevalence of OSMF in the Indian subcontinent owing to increased consumption of smokeless tobacco products. Very few cases of pediatric OSMF are reported in PubMed literature. Oral submucous fibrosis has a malignant transformation rate of 7–13% and hence, it is important to intervene at an appropriate stage and manage it well in time. Aim and objective To report a case of oral submucous fibrosis (OSMF) in a 6-year-old Indian girl along with its management and follow-up. Case description A 6-year-old girl of Indian origin was diagnosed with OSMF and we have used sesame oil pulling as a novel treatment approach and observed good results with long-term follow-up. We have also reviewed PubMed literature for cases of pediatric OSMF reported till date. Conclusion A timely diagnosis and intervention becomes necessary in pediatric OSMF to improve oral function and prevent malignant transformation. Clinical significance It is important to report oral potentially malignant disorder (OPMD) cases in pediatric patients and create awareness through health education programs so that parents and children know about the ill effects of consuming tobacco products. How to cite this article Gupta S, Gupta S, Chaudhary C, et al. Novel Treatment Approach of Oral Submucous Fibrosis in a 6-year-old Girl: A Case Report. Int J Clin Pediatr Dent 2021;14(4):575–579.