Introduction Post-operative sore throat (POST) is a common complication after endotracheal intubation, influenced by various factors. Dexamethasone, an anti-inflammatory, and dexmedetomidine, an alpha-2 adrenergic agonist, have both been studied for POST prevention. This trial compared their efficacy in patients undergoing laparoscopic cholecystectomy.  Materials and Methods In this two-year, double-blind, randomized trial, 60 adults undergoing elective laparoscopic cholecystectomy were divided into two groups: Group 1 received dexamethasone (0.2 mg/kg, max 8 mg), and Group 2 received dexmedetomidine (1 µg/kg). POST incidence and severity were assessed, with statistical significance set at p<0.05. Results No significant differences were found in age, gender, or BMI between the groups. Group 2 showed lower heart rates and MAP post-intubation. POST incidence was 33.33% in Group 1 and 46.66% in Group 2 (p=0.354), with comparable POST severity and complications. Conclusion: The incidence and severity of post-operative sore throat and hoarseness were similar while using dexamethasone and dexmedetomidine in patients undergoing elective laparoscopic cholecystectomy under general anaesthesia.