More than 87% of the Colombian population lives in zones of intermediate and high seismic hazard, which has generated an increasing interest toward base isolated structures. Nowadays, this technique has been mainly applied to hospitals and bridges. However, it is necessary to expand the action field of isolators to diverse kind of structures in countries with high seismic hazard. In this direction, the performance of circular unbounded fiber reinforced elastomeric isolators (U-FREI) was studied in a two degrees-of-freedom (DoF), medium scale structure, under seismic excitation. This evaluation was achieved employing a Real-Time Hybrid Simulation (RTHS), which is defined as a modern cyber-physical technique used for the experimental evaluation of complex systems, that treats the system components with predictable behavior as a numerical substructure, and the components that are difficult to model as an experimental substructure. In this case, the main structure was considered as the numerical substructure and a couple of U-FREI was treated as the experimental substructure. The RTHS was evaluated using a set of Current Assessment Measurements, where an accurate tracking of the transfer system was determined. Furthermore, the experimental results were compared with Shaking Table Tests (STT) developed at University of Naples Federico II. Particularly, peak and RMS comparison of force and acceleration signals showed a similar behavior of the RTHS according to the STT results. Overall, both approaches demonstrated that the U-FREI were able to reduce more than the 70% of the structural drift with respect to the fixed structure, and the applied RTHS methodology was verified.