While chemically similar to numerous other high explosives, pure diethylene glycol dinitrate is difficult to ignite or detonate.

DEGDN can be mixed with nitrocellulose or nitroglycol to form a colloid, which is used in smokeless powder for artillery and rocket propellant.

If ingested, like nitroglycerine, it rapidly causes vasodilation through the release of nitric oxide, a physiological signaling molecule that relaxes smooth muscle.

[clarification needed] Consequently, diethylene glycol dinitrate has occasionally been used medically to relieve angina, which is substernal chest pain associated with impaired cardiac circulation.

The medical application was never widespread, the standard nitroglycerine being faster acting and very inexpensive; oral nitrates in any case being only palliative, not an effective treatment.