Background: Premedication before general anesthesia aims to alleviate anxiety, facilitate smooth induction, and improve perioperative outcomes. While benzodiazepines like alprazolam are commonly used, they may cause sedation-related side effects. Melatonin, a naturally occurring hormone with sedative and anxiolytic properties, has emerged as a potential alternative with a favorable safety profile. Aim: To compare the efficacy and safety of oral melatonin versus oral alprazolam as premedication in adult patients undergoing various elective surgical procedures under general anesthesia. Methodology: 60patients with ASA I–II, aged 18–60 years, scheduled for elective surgeries under general anesthesia, were randomly assigned into two equal groups (n = 30). Group M received 3 mg of oral melatonin, and Group A received 0.5 mg of oral alprazolam, administered 120 minutes before surgery. Preoperative assessments included heart rate (HR), blood pressure (BP), oxygen saturation (SpO₂), anxiety levels (measured using Visual Analogue Scale – VAS), and sedation levels (assessed using Ramsay Sedation Score). All parameters were recorded at baseline (before drug administration) and again two hours after drug intake. Results: Melatonin significantly reduced preoperative anxiety scores compared to alprazolam (VAS score: 2.5 ± 0.8 vs. 3.9 ± 1.1, p< 0.001). Hemodynamic parameters remained more stable in the melatonin group, with fewer fluctuations in HR and BP compared to the alprazolam group (p = 0.03). Sedation levels were adequate in both groups; however, melatonin produced a more physiologically stable sedation profile and was associated with significantly less postoperative drowsiness (p = 0.02). Conclusion: Oral melatonin (3 mg) is superior to alprazolam (0.5 mg) in reducing preoperative anxiety while maintaining better hemodynamic stability and causing fewer sedative side effects. These findings suggest melatonin as a safer and more effective alternative to benzodiazepines for preoperative anxiolysis.