Introduction: Hyperglycemia is a characteristic feature of the metabolic response to surgery. A prospective randomized observational study was conducted to compare the efficacy of dexmedetomidineand fentanyl in attenuating the neuroendocrine stress response by measuring serial random blood sugar level in patients undergoing laparoscopic cholecystectomy.Methodology: 40 patients of ASA physical status I or II of either sex, aged between 35–65 yrs scheduled to undergo laparoscopic cholecystectomy under general anaesthesia were randomly divided by envelope method into one of the 2 groups of 20 patients each (group D and group F). Patients allocated in group D patients (n = 20) were given IV infusion of dexmedetomidine 1μg/kg in 100 ml normal saline and Group F patients (n = 20) were given IV infusion of fentanyl 2 μg/kg in 100 ml normal saline over a 15 min period before the induction of general anaesthesia. Serial random blood sugarestimation was done perioperatively. Heart rate (HR), Oxygen saturation (SPO2), systolic blood pressure (SBP),  diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded at various time intervals. Results: It was observed that blood glucose concentration increased in both the groups and the increment being more distinct in group F. 5 minutes post extubation, the mean random blood sugar value in group D was clinically lower compared to that in group F and it was statistically significant (p<0.001). The heart rate, systolic and diastolic blood pressure and mean arterial pressure was significantly lower in group D when compared to group F. Conclusion: We conclude that dexmedetomidine is more effective than fentanyl in reducing the neuroendocrine and hemodynamic stress responses during laparoscopic cholecystectomy.