This paper deals with active mode localization control of a periodic structure comprising a series of coupled identical components. Once mode localization occurs, vibration energy normally distributed throughout a whole system is intensively concentrated in a particular component of a periodic system, and hence needs to be eschewed because of localized stress. This paper begins by elucidating the causes of the mode localization phenomenon which is likely to happen in a periodic structure under some conditions. Numerical analysis is then performed, investigating the mode localization phenomenon from a viewpoint of dynamical compliances as well as mode behavior of a total system comprising coupled flexible beams with springs. It is shown that energy confinement in terms of disturbance forces takes place when mode localization takes place. In consideration of the energy confinement, active mode localization control is presented, enabling the vibration isolation from the disturbance energy. Finally, an experiment is carried out, demonstrating the validity of the proposed method for the purpose of actively isolating power flow form one subsystem to another.