The present study deals with the seismic response of three-leaf stone masonry subassemblies before and after the application of intervention techniques. In detail, shaking table tests are performed on a scaled substructure in the Laboratory for Earthquake Engineering, at the National Technical University of Athens (NTUA). The substructure consists of two parallel walls. One wall is of rectangular section, whereas the other is provided with a portion of transverse wall at its mid-length. A flexible timber floor rests on the top of the walls. Sine-sweep and dynamic tests are performed perpendicular to the two walls, before and after interventions. The aim of this work is to experimentally study the response of three leaf masonry walls against in-plane and out-of-plane seismic actions, to investigate the effect of the transverse wall to the out-of-plane behavior of walls (and vice versa) and to assess the effect of a selected set of interventions on the behavior of the substructure. The results of this study confirm the vulnerability of three leaf masonry structures, evidenced by the premature detachment of masonry leaves. They prove the significant role of the transverse wall, in reducing the width of the separation cracks observed in the walls subjected to out-of-plane actions followed by an increase of its in-plane damage, as well as the positive effect (in terms of load and deformation capacity) of grouting the walls and enhancing the diaphragm action of the floor. Additionally, the experimental results of this study can serve as a validation tool for the calibration of numerical models and as input for further analytical research. In this paper, the calibration of a smeared crack model that is based on macro-modeling approach is presented, along with a comparison between experimental and numerical results for the specimen before interventions, based on the performed calibration.