Introduction: The haemodynamic response to anaesthetic induction with endotracheal intubation may be harmful in patients with cardiovascular disease, increased intracranial pressure, or anomalies of cerebral vessels. Objective: A comparative study for attenuating reflex hypertension and tachycardia by using oral administration of Clonidine and Melatonin before induction of general anaesthesia. Methods: After obtaining the institutional ethical approval total of 76 patients scheduled for gastro-intestinal surgeries under general anaesthesia were divided into 2 groups, Group 1( 38 patients) received oral Melatonin 6 mg tab before surgery and Group 2 (38 patients) received oral Clonidine 100mcg before surgery. Heart rate, Systolic blood pressure(SBP), Diastolic blood pressure (DBP) and Mean arterial pressure (MAP) were recorded in two groups at different point of time i,e before premedication, immediately before induction, after tracheal intubation and every 3 min thereafter for 15 min. Incidence of perioperative and postoperative complications in 2 groups was also observed. Result: The results of observation were compiled, tabulated and statistically analyzed using the Chi-square test and unpaired t-test as and where applicable. Oral Melatonin was found better than oral Clonidine in lowering Systolic blood pressure(SBP), Diastolic blood pressure (DBP) and Mean arterial pressure (MAP) and heart rate changes associated with laryngoscopy and intubation. Occurrence of peri and postoperative complication in both the groups which were mild. Conclusion: From the observation of the present study, it can be concluded that oral Melatonin is a better agent than oral Clonidine in maintaining haemodynamic stability during gastrointestinal surgery under general anaesthesia.