Denaturation is a structural change in biomolecules such as nucleic acids and proteins, usually caused by heat, acids, bases, detergents, or certain chemicals such as urea.

Proteins denature when they lose their three-dimensional structure and thus their characteristic folded structure. Enzymes lose their catalytic activity, because the substrates can no longer bind to the active site. Some, but not all, proteins can regain their correct structure when the denaturing influence is removed.

The denaturation of nucleic acids such as DNA, also called melting, is the separation of a double strand into two single strands, which occurs when the hydrogen bonds between the strands are broken. Nucleic acid strands realign when "normal" conditions are restored.

Denaturation can also refer to the intentional adulteration of ethyl alcohol so that it is unsuitable as a beverage. Please see main article: Denatured alcohol.

Denaturation is also the transformation of fissile material suitable for nuclear weapons into a form that is not suitable for that and can not easily be reversely transformed. For U-235 this is easy, by mixing it with U-238, but for plutonium it is more difficult and/or less effective, because other plutonium isotopes are either also suitable for weapons or not available and not practicle to produce, while mixing with another element allows chemical separation.