Introduction: Hypertonic saline (HS) has an important role in the treatment of raised intracranial pressure after traumatic brain injury. This study evaluates the efficacy and safety of HS and its impact on the postoperative course of patients undergoing craniotomy for low-grade gliomas. Materials and Methods: Sixty patients with supratentorial low-grade glioma were enrolled. All patients were anesthetized and operated with the same team and protocol. They successively received either HS or mannitol just before surgery. The amount of brain edema was classified according to the dural tension score (I–III) just after craniotomy and before dural opening. Other intraoperative measurements (such as urine output, need, and dosage of other diuretic agents) and postoperative findings (intensive care unit [ICU] and hospital stay, corticosteroid demand, and confusion period) were also assessed. Pre- and postoperative serum S100B levels were documented in both groups. Results: The dural tension score was not significantly different among the two groups: severe tension in six and five patients in the mannitol and HS groups, respectively. HS group had a significantly lower amount of diuresis (609 vs. 725 ml) during surgery. Patients in the HS group had shorter ICU stay (16.3 vs. 27.9 h) and shorter duration of corticosteroid therapy after surgery (3.4 vs. 5.2 days). Conclusion: HS infusion just before the onset of craniotomy is at least as effective as mannitol in controlling intraoperative brain edema in patients with supratentorial glioma. Improved early postoperative course and lower degrees of S100B rise after craniotomy seen in the HS group needs to be explained in more detailed studies.