Background: Oral submucous fibrosis (OSMF) is a premalignant condition prevalent in our country. Juxtaepithelial inflammation with progressive hyalinization of the lamina propria results in stiffness and fibrosis of the oral mucosa, characterised by trismus, ankyloglossia, and a burning sensation. Various methods of treatment have been tried in these cases, which include placental extract injections and the cutting of fibrous bands. In this study, we aim to compare the outcome of intra-lesional placental extract injection with fibrotomy and placental extract gel application in OSMF.Methodology: This prospective interventional study included 58 patients clinically diagnosed with OSMF grades II and III at a rural tertiary care hospital between January 2021 and August 2022. The patients were randomised into two groups: group I received 1 ml of intra-lesional human placental extract injection in the submucosal plane of the buccal mucosa and retro-molar trigone (RMT) once a week for five consecutive weeks, and group II was subjected to a transverse division of fibrotic bands in the submucosal plane under general anaesthesia. The surgical wound was left open, and swabs soaked in human-purified placental extract gel were placed in the wound for two hours twice daily until the surgical wound was epithelialized and healed. The patients in both groups I and II were advised to do jaw opening exercises, and weekly follow-up was done. Findings with regard to maximum mouth opening, colour of mucosa, and burning sensation in the oral cavity based on a Likert scale were documented. At the end of five months, the pre-treatment and post-treatment results documented were compared.Results: All patients were between 20 and 60 years of age and were addicted to chewing areca nuts with tobacco. Bilateral involvement was present in all patients, with extension into the RMT and soft palate seen in 31%. Improvement in mouth opening was between 4 mm and 6 mm in group II, and relief of burning sensation and mucosal colour was better in group I.Conclusion: Intra-lesional placental extract injections help in the improvement of the mucosa and relief from the burning sensation. Fibrotomy with placental extract gel application is better at relieving trismus in OSMF. Aggressive mouth-opening exercises may improve mouth opening following the above procedures.