An approach is suggested for treating multiscale fluctuations in macromolecular systems. The emphasis is on the statistical, properties of such fluctuations. The approach is illustrated by a macromolecular system with mesoscopic fluctuations between the states of atomic orbitals Strong orbital and weak orbital couplings fluctuation ally arise, being multiscale in space and time Statistical properties of the system are obtained by averaging over the multiscale fluctuations. The existence of such multiscale fluctuations causes phase transitions between strong coupling and weak coupling states. These transitions are connected with structure and size transformations of macromolecules. An approach for treating density and size multiscale fluctuations by means of classical statistical mechanics is also advanced.