The most valuable substance in the Dune universe is called melange , commonly referred to as "the spice." It is a rare, highly prized drug found only on the desert planet Arrakis (also called Dune). Melange provides users with a longer lifespan, increased vitality, heightened awareness, and in some cases, prescient abilities that enable safe interstellar travel. Its value is immense, making it the central commodity in the Dune universe's economy and politics, and it is highly addictive with fatal withdrawal. The spice gives the users distinctive blue-within-blue eyes, known as the "Eyes of Ibad," especially seen among the native Fremen people. Harvesting the spice is perilous due to the giant sandworms that inhabit Arrakis, making it a substance of great power and scarcity.

In short, the valuable substance in Dune is the spice melange.