Introduction: Postoperative sore throat (POST) is a common cause of distress and dissatisfaction after general anesthesia. POST is one of the most distressing symptoms after general anesthesia. Incidence of POST ranges from 14.4% to 90% following laryngoscopy and tracheal intubation. Various drugs with different routes are examined to prevent POST. We intended to compare the effectiveness of nebulized dexamethasone and magnesium sulfate (MgSO4) in decreasing the incidence and severity of POST. Materials and Methods: In this prospective double-blind study, adult patients with either sex undergoing laryngoscopy and intubation for surgery were randomly assigned into dexamethasone (Group D) and MgSO4 (Group M). The primary outcome was to assess incidence and severity of POST, and secondary outcome was to assess the incidence of hoarseness and cough. Continuous variables were presented as mean ± standard deviation, and t-test was applied for comparing the difference of means between the two groups. P ≤0.05 was considered statistically significant. Results: The incidence of POST in Group D was much lower as compared to Group M at 0 h (P = 0.0262), but after that, there was no significant difference between groups. Severity of POST was compared between Group D and Group M at 0, 4, 8, 12, and 24 h postoperatively. At 0 h, Group D had 22 patients with no pain at rest (Grade 0) whereas Group M had 12 patients. The secondary outcomes (pain at deglutition, hoarseness, and cough) at 0, 4, 8, 12, and 24 h were not statistically significant (P > 0.05). Conclusions: Preoperative MgSO4 nebulization is as effective as dexamethasone nebulization in decreasing the incidence and severity of POST without causing any adverse effect. Incidence of pain on deglutition, hoarseness, and cough are also reduced effectively by both drugs.