Mannitol is used intravenously to reduce acutely elevated intracranial pressure until more definitive therapy can be applied, [14] eg, after head trauma. Although mannitol injection is the mainstay of treatment for cranial hypertension after severe brain injury, it is no better than hypertonic saline as a first-line treatment. In refractory cases, hypertonic saline works better. [15] Intraarterial infusion of mannitol can temporarily open the blood-brain barrier by disrupting tight junctions. [16] [17]

It is also used in some cases of kidney failure, less urine output, lowers eye pressure, increases removal of certain toxins, and treats fluid accumulation. [7]

Intraoperative mannitol before vascular clamp release during kidney transplantation has been shown to reduce post-transplant kidney injury but not graft rejection. [medical citation required]

Mannitol is used as an osmotic laxative[2][18] in oral doses greater than 20 g,[19] and is sometimes sold as a laxative for children. [citation needed]

The use of mannitol, when inhaled, as a bronchial irritant has been proposed as an alternative method for diagnosing exercise-induced asthma. A 2013 systematic review concluded that there is currently insufficient evidence to support its use for this purpose.

Mannitol is commonly used in cardiopulmonary machine cycle priming during cardiopulmonary bypass. The presence of mannitol protects renal function during periods of low blood flow and stress while the patient is in a bypass state. This solution prevents swelling of the kidney's endothelial cells, which could reduce blood flow to the area and cause cell damage.

Mannitol is also used to temporarily coat a sharp object (such as the helix on an artificial pacemaker lead) as it passes through the venous system. Because mannitol dissolves easily in the blood, the sharp tip is exposed to its destination.