Background: I-gel is a supraglottic airway device (SGAD) in the second generation offers reduced air passage complications in contrast with other SGADs with inflatable cuffs. Propofol combined with opioids facilitates its insertion. This study aimed to compare dexmedetomidine and fentanyl pre-treatment for i-gel insertion under propofol anesthesia in terms of jaw relaxation, hemodynamic stability, and overall insertion conditions. Methods: Methods: In this prospective, randomized trial, 60 individuals (18–60 years old, ASA I–II) were allocated at random to undergo anesthesia with either 1 μg/kg of fentanyl or 1 μg/kg of dexmedetomidine, followed by 2 mg/kg of propofol. Jaw relaxation, hemodynamic parameters (modified Lund and Stovener scheme), and propofol requirement were assessed. Results: Both groups achieved comparable I-gel insertion conditions (excellent in 66.7% with fentanyl and 63.3% with dexmedetomidine). However, dexmedetomidine showed a significantly lower mean heart rate compared to fentanyl. Propofol requirements were slightly higher in the fentanyl group (2.03 vs. 1.40 mg/kg). Conclusions: Comparable general conditions are offered by fentanyl and dexmedetomidine for i-gel insertion with propofol. While both offer hemodynamic stability, dexmedetomidine exhibits superior attenuation of the heart rate response and reduced propofol requirement, potentially leading to improved patient outcomes. © 2024 Elsevier B.V., All rights reserved.