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We present the results of a large-scale experimental campaign performed on the prototype structure of EuroProteas in Thessaloniki, Greece, to assess the effectiveness of gravel-rubber mixture (GRM) layers underneath shallow foundations as a means of geotechnical seismic isolation (GSI). We found that the geotechnical seismic isolation of structures is optimized by increasing the rubber content of the soil rubber mixture up to 30% per mixture weight. Although the effectiveness of the GSI systems has been investigated numerically and in small-scale experiments, this paper seeks to fill the gap in the lack of full-scale experimental studies on this subject. Three soil pits were excavated and backfilled with GRM of different rubber content per weight to serve as foundation soil for the structure. A large number of instruments were installed on the structure, the foundation, the soil surface, and inside the gravel-rubber mixture layers beneath the foundation to fully monitor the GSI-structure systems' response in three dimensions. The experimental investigation included ambient noise, free-and forced-vibration tests. Our results showed that a geotechnical seismic isolation layer composed of a gravel-rubber mixture with 30% rubber content per weight effectively isolates the structure. Even 0.5m thickness (i.e., B/6 of the foundation width) of the GSI system is successfully cutting off practically all emitted waves at a (horizontal or vertical) distance of B/6 from the foundation. A significant reduction in the GSI-structure system's stiffness was apparent, leading to a rocking-dominant response. The rise in the system's damping and the substantial energy dissipation inside the GRM layer highlight its effectiveness as a geotechnical seismic isolation system.