Introduction: This study aimed to compare the effects of dexmedetomidine and clonidine in attenuating the sympathoadrenal response during laryngoscopy and intubation in patients undergoing surgery. Methods: A randomized controlled trial was conducted on 100 patients, divided into two groups: dexmedetomidine group (n=50) and clonidine group (n=50). Hemodynamic parameters including heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were recorded before induction, after induction, after laryngoscopy and intubation, and 5 minutes thereafter. The data were analyzed using appropriate statistical tests. Results: The results revealed that both dexmedetomidine and clonidine significantly attenuated the sympathoadrenal response during laryngoscopy and intubation compared to baseline values. However, dexmedetomidine showed a more pronounced effect in reducing heart rate and blood pressure parameters compared to clonidine. Specifically, the dexmedetomidine group exhibited a lower heart rate and blood pressure at all measured time points compared to the clonidine group. Conclusion: Dexmedetomidine and clonidine are effective in blunting the sympathoadrenal response during laryngoscopy and intubation. However, dexmedetomidine demonstrates superior efficacy in maintaining hemodynamic stability compared to clonidine. These findings suggest that dexmedetomidine may be a more favorable choice for attenuating the hemodynamic response to laryngoscopy and intubation in surgical patients.