Background and Aim Oral cancer is one of the most preventable cancers with a typical sequence of emergence as a potentially malignant disorder promotion and transformation into cancer. Oral submucous fibrosis OSMF is a potentially malignant disorder in which the mucosa stiffens and patients have trouble opening their mouth thus affecting their quality of life. Early therapeutic intervention yields better results. However oral submucous fibrosis has never been successfully treated by any single medication so far. Practitioners have tried various combinations of the drugs with variable results. Hence we conducted this meta-analysis to assess which treatment modality gives a better result with regard to improvement in mouth opening in OSMF patients.Methods Electronic search for articles published in various journals were undertaken through various search engines till October 2021. About 29 articles were selected which had performed randomized control trials of various drugs on oral submucous fibrosis. Frequentist network meta-analysis was performed using R studio software and effective treatment ranking was derived.Results According to the treatment ranking generated relative to mouth opening the most effective treatment was the intralesional steroid and hyaluronidase with vitamin E supplementation and the intralesional steroid and hyaluronidase with lycopene being the second best.Conclusion This network meta-analysis has analyzed the efficacy of various drug regimens used in the management of oral submucous fibrosis which can be implemented by the practitioners in the management of initial stages of oral submucous fibrosis thus preventing its progression into oral cancer.