Background: Smooth extubation is a critical component of postoperative airway management, especially in patients undergoing functional endoscopic sinus surgery (FESS). The avoidance of adverse events, such as coughing, laryngospasm, or hemodynamic instability, is paramount in ensuring patient safety and optimal recovery. This review examines the efficacy and safety of intratracheal dexmedetomidine versus lidocaine in facilitating smooth extubation in FESS patients, highlighting their pharmacological profiles, clinical outcomes, and practical applications. Dexmedetomidine, an alpha-2 adrenergic agonist, is known for its sedative, analgesic, and sympatholytic properties. It reduces the stress response associated with extubation and promotes hemodynamic stability. Lidocaine, a local anesthetic, effectively suppresses airway reflexes and minimizes coughing during extubation. Both agents have distinct mechanisms of action, which influence their role in airway management during the peri-extubation period. Several studies have compared the intratracheal administration of dexmedetomidine and lidocaine for smooth extubation in FESS. Dexmedetomidine has demonstrated superior control over hemodynamic parameters, reduced the incidence of postoperative agitation, and enhanced patient comfort. Conversely, lidocaine is effective in minimizing coughing and laryngospasm, making it a reliable choice for managing hyperreactive airways. Both agents contribute to minimizing adverse extubation outcomes, although their efficacy may vary based on individual patient characteristics and clinical scenarios. Dexmedetomidine’s longer duration of action and sedative effects may be advantageous for patients requiring stable recovery, but it can potentially prolong extubation time in some cases. Lidocaine’s rapid onset and targeted airway effects make it suitable for short-term control of airway reflexes; however, its limited systemic effects may not provide the same level of hemodynamic stability as dexmedetomidine. The choice between intratracheal dexmedetomidine and lidocaine for smooth extubation in FESS patients should be guided by patient-specific factors, surgical complexity, and the desired clinical outcomes. While both agents effectively contribute to smooth extubation, dexmedetomidine offers a broader range of benefits, including sedation and hemodynamic control, whereas lidocaine provides targeted airway reflex suppression. Future research, including large-scale randomized trials, is needed to establish definitive guidelines for selecting the optimal agent in various clinical scenarios.