UnReinforced Masonry (URM) constitutes a significant portion of the historical building stock across Mediterranean regions, particularly in seismic-prone areas. Due to its heterogeneous and non-engineered nature, especially when built with natural stones and poor mortar, URM exhibits high seismic vulnerability, making its assessment and retrofit a pressing concern. A wide experimental campaign was conducted at the EUCENTRE Foundation and the University of Pavia (Italy), including vertical and diagonal compression tests on wallettes and in-plane cyclic shear-compression tests on piers, with or without surface jacketing applied to one or both sides. This study focuses on the in-plane mechanical behavior of natural stone URM structures through diagonal compression tests. The experimental results were used to calibrate a numerical model developed in OpenSees, using a macro-modelling approach. The simulation accurately replicated the stiffness, strength, and crack patterns observed in the tests. The validated numerical model sets the groundwork for subsequent analyses of stone masonry elements and structures under different geometric, boundary, and retrofit conditions, contributing to the broader effort of enhancing the resilience of heritage masonry structures while preserving their cultural and architectural value.