Background and objective: Tracheal intubation is considered to represent a major cause of trauma to the airway mucosa, which can give rise to a postoperative sore throat. This randomized clinical quality improvement trial on the well-established benefit of gargling with licorice extract, ketamine, and magnesium sulfate before laryngoscopy and tracheal intubation was undertaken to address how to prevent throat soreness, hoarseness, and cough. Patients and methods: In a prospective, double-blind randomized controlled trials, 105 patients who were undergoing laryngoscopy and endotracheal intubation under general anesthesia were recruited. They were assigned into one of three intervention groups, including ketamine, licorice, and magnesium sulfate, using block randomization and requested to gargle twice for 15 seconds and 20 minutes before anesthesia induction and to spit out. Postoperative sore throat, cough, and hoarseness were recorded from endotracheal extubation at baseline (T0) every 10 minutes during recovery until T45 (45 minutes) and at initial 24-hour time points (2, 4, 8, 12, and 24 hours) later. Analysis of variance (ANOVA) and chi-squared tests was used for data analysis at a significance level of p = 0.05 in Statistical Package for the Social Sciences (SPSS) v20 (Chicago, Illinois, United States of America) software. Results: The mean age of patients was 48.21 ± 9.21 years, and 57.1% were male. No statistically significant intergroup difference was observed in the study groups for oxygen saturation (SpO₂), heart rate, blood pressure, and duration of surgery. Our results showed that less sore throat was found in the ketamine group at T8/T12 (8 and 12 hours after recovery (p < 0.05). In addition, no statistically significant intergroup difference was revealed in cough and hoarseness during the times studied (p > 0.05). Conclusion: Our evidence confirmed that ketamine, licorice, and magnesium sulfate appeared to be able to effectively reduce pain, cough, and hoarseness and to be associated with similar hemodynamic changes, while the ketamine-treated subjects manifested a marked decrease in sore throat pain intensity with postoperative times of T8 and T12. Consequently, gargling with ketamine continues to demonstrably be put forward as a promising candidate to control postoperative sore throat but is as equal as other intervention drugs in terms of effectively controlling cough or hoarseness. Ultimately, the final choice relies on both patient acceptance and anesthesiologist preference.