Background: Many drugs have been used for attenuating hemodynamic response to intubation and laryngoscopy during general anesthesia, to provide post operative analgesia and to decrease the analgesic consumption in post operative period. The present study was conducted to evaluate the effects of low dose Melatonin and Alprazolam combination in patients undergoing laparoscopic cholecystectomy under general anesthesia. Materials and Methods: Fifty adult patient of either sex, aged between 20­ 50 years with American Society of Anesthesiologist (ASA) grade I and II presenting for laparoscopic cholecystectomy were divided into two groups. Group I (Gp I, n=25) acted as a control group and received placebo as tablet B complex and Group II, (test group Gp II, n=25) received Tab. Melatonin (3mg) and Alprazolam (0.25mg) combination one hour before surgery. The primary objectives were to assess the sedation score, effect on induction dose of Propofol and hemodynamic response to laryngoscopy and intubation. Secondary objectives were to assess the post operative Fentanyl consumption in first 24 hours. Statistical Analysis: The data thus obtained was analyzed using Epi­info and SPSS 16 software and various suitable statistical tests like Student t test, ANOVA, Chi­square test, Mann Whitney test etc. were applied. P­values > 0.05 were considered to be not significant, p­values <  0.05 were considered to be significant and p­values < 0.001 were considered to be highly significant. Results: The level of sedation in Gp II was significantly higher as compared to Gp I at one hour of giving the test drug(0.88±0.332 vs. 0.00±0.00, p value <0.001). The mean dose of Propofol for induction of general anesthesia was significantly reduced in Gp II (109.20±17.540 in Gp I and 87.60±17.388 in Gp II respectively, p value< 0.001). Both groups showed rise in heart rate and mean blood pressure following laryngoscopy and intubation up to three minutes but the rise was significantly more in Gp I as compared to Gp II at all time intervals . Significant decrease in total number of doses (5.12 ±0.833 vs. 4.12±0.332, p<0.001) as well as mean total fentanyl consumption (316.88 vs. 246.86, p<0.001) was noted in Gp II. No adverse effect was noted during the study which can be attributed to test drug. Conclusion: Low dose melatonin and alprazolam combination when given one hour before the surgery provides many advantages. It produces sedated patients which are easily arousable, decrease dose of induction agent, decrease the increase in heart rate and mean arterial blood pressure following laryngoscopy and intubation. It also reduces the post operative fentanyl consumption in first twenty four hours following surgery.