Background: Submucous fibrosis with a high incidence rate in the Indian subcontinent is a devastating disease affecting the oral cavity and oropharynx. Aims and Objective: To evaluate the efficacy of injection placentrex and injection hydrocortisone in oral submucous fibrosis patients in increasing mouth opening, burning sensation, and improve the mucosal lining. Materials and Methods: We recruited 60 patients with Stage II and Stage III of the ailment, who were randomly divided into Group A and Group B. They were administered submucosal injections of hydrocortisone and placentrex along with physiotherapy and oral iron, nutrients, and B-carotene supplements over a period of 2 months. Interpretations and Results: The pinnacle rate of the incidence was found in the age group of 30 to 40 years among both the genders. Statistically significant difference ( P = 0.0001), that is, 5.19 ± 1.33 in Group A and 11.69 ± 1.26 mm in Group B was noted in the mean mouth opening values. Statistically significant difference in burning sensation was noted to be better in Group A than in Group B. Discussion and Conclusion: Overall hydrocortisone seems to be a better regimen for improving the mucosal health and increasing the mouth opening as compared to placentrix regimen. Although Placentrex is better than hydrocortisone in reducing burning sensation.