Introduction: The surgical removal of impacted mandibular third molars is an invasive procedure that involves extensive tissue trauma and a considerable postoperative inflammatory response. Although the inflammatory process is necessary for healing when exacerbated it may cause pain, swelling and limited mouth opening. Corticosteroids are among the most widely employed pre-operative medication administered for the control of such complications. Objective: To compare the effects of single dose of pre-operative Injection Dexamethasone versus Injection Methylprednisolone via Intramuscular or Submucosal route for controlling the post-operative pain, swelling and limited mouth opening in the removal of impacted mandibular third molars. Material and Method:. The present study was conducted on 40 healthy adult patients with bilaterally symmetrical impacted mandibular third molar, reporting to the Department of oral and Maxillofacial Surgery of Guru Nanak Dev Dental College and Research Institute, Sunam. Clinically, pain, swelling, mouth-opening were evaluated pre-operatively as baseline and post-operatively on 1st, 3rd and 7th post-operative days. Results: The results of our study are summarized below: In Group A: Submucosal injection of dexamethasone gave better results in controlling pain, swelling and trismus in comparison to Intramuscular injection of dexamethasone. In Group B: Submucosal injection of methylprednisolone showed better results in terms of pain, swelling and trismus when compared with Intramuscular injection of methylprednisolone. In Group C: Intramuscular injection of dexamethasone gave better results in terms of pain and mouth opening but, swelling was reduced with Intramuscular methylprednisolone. In Group D: Submucosal injection of dexamethasone showed better results in terms of pain, but swelling and mouth opening was reduced when methylprednisolone was used submucosal. Conclusion: The results of our study concluded that Dexamethasone is better than Methylprednisolone in controlling post-operative sequelae after third molar surgery. This can attributed to the higher potency and longer half-life and less sodium retaining capacity of dexamethasone than methylprednisolone. The results of our study also concluded that submucosal route of administration of drug is better than Intramuscular route because of the repository effect of the submucosal route, also this route is beneficial to the patient as well to the surgeon because needle penetration is done in the pre-anesthetized area, also it is an easy technique to be mastered by the surgeon.