Objectives: Surgical intervention for removal of an impacted third molar can lead to significant pain and swelling. Corticosteroids show promise for mitigating postoperative sequelae across various surgical contexts. The use of corticosteroids following minor oral surgery, though controversial, has already been proven effective. However, little research has explored peroral prescription of corticosteroids despite its convenience for outpatients and for non-surgeons like implantologists and periodontists and others who don’t have access to needle injections. The aim of this study was to address a void in the literature by comparing the effects of two styles of preoral administration of prednisolone after surgical removal of the mandibular third molar and to determine which style minimizes postoperative sequelae. Materials and Methods: A randomized, split-mouth clinical study was conducted to investigate the efficacy of two different styles of preoral prednisolone in mitigating postoperative sequelae following surgical extraction of impacted mandibular third molars. Fifteen participants were enrolled in the study. Random selection was used to determine the prescription style for the right and left mandibular arch. Group A included those who received a single dose of prednisolone 25 mg, while group B received prednisolone 5 mg postoperatively for a period of three days (5 mg three times/day on the first postoperative day, 5 mg twice/day on the second postoperative day; 5 mg once/day on the third postoperative day). Results: There was a significant difference in the distance between the corner of the mouth and tragus, which decreased with the time interval with respect to group B when compared to group A. Conclusion The present study showed that a three-day tapered dose of prednisolone postoperatively was more effective in reducing post-extraction sequelae than a single-dose regimen.