In many cases, denaturation is reversible. Since the primary structure of protein is intact, once the denaturing influence is removed, proteins can regain their native state by folding back to the original conformation. This process is called renaturation.

However, denaturation can be irreversible in extreme situations. The denatured protein is unable to return to the native, biologically functional state even after removing the denaturing agents. This irreversibility is typically a kinetic, not thermodynamic irreversibility, where the protein is stuck in a local minimum energy state that stops it from refolding back to the original state.