Background: Different agents have been used to control postoperative sore throat after general anesthesia with variable success. The aim of this study was to compare the effect of preoperative-nebulized magnesium sulfate versus lidocaine on the prevention of post-intubation sore throat. Methods: A prospective double-blind randomized controlled study. Seventy-eight patients were divided randomly into three equal groups: Group (M) (n = 26): received nebulized magnesium sulfate 250 mg (2.5 ml) plus 2.5 ml normal saline. Group (L) (n = 26): received nebulized lidocaine 2% 100 mg (5 ml). Group (C) (n = 26): received nebulized normal saline 5ml. So total volume (5 ml). Patients nebulized by compressor nebulizing for 15 min before the induction of anesthesia. Results: At 0 and 2 h postoperative, the severity and incidence of sore throat were statistically significantly lower in group M and L compared to the C group (P < 0.001). However, at the same time interval, both groups M and L were comparable (P > 0.05). At 4, 8, 12, 24 h postoperative, the severity and incidence of sore throat were statistically significantly lower in group M compared to L and C groups (P < 0.001). However, at the same time interval, both groups L and C were comparable (P > 0.05). The hemodynamics was statistically significantly reduced in group L compared to M and C groups. However, group M showed statistically insignificant changes in hemodynamics compared to groups L and C. Conclusions: Preoperative 250 mg nebulized magnesium sulfate has more protection against post-intubation sore throat than 100 mg nebulized lidocaine lasting up to 24 h after the operation.