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This paper presents an experimental and numerical study on different retrofit solutions for stone masonry buildings with timber diaphragms in earthquake-prone regions, aiming at enhancing wall-to-diaphragm connections, diaphragms’ stiffness, and masonry properties. The experimental results of incremental dynamic shake-table tests on three full-scale two-story buildings, complemented by material and component characterization tests, are initially summarized. The first building specimen was unstrengthened. The second one was retrofitted at the floor and roof levels with improved wall-to-diaphragm connections and a moderate increase in diaphragm stiffness. Connections were also improved in the third specimen together with a significant enhancement of diaphragm stiffness. The calibration of two numerical models, versus the experimental response of the retrofitted building specimens, is then presented. The models were further modified and reanalyzed to assess the effects of masonry mechanical upgrades, which could be achieved in practice through deep joint repointing or various types of jacketing. These solutions were simulated by applying correction coefficients to the masonry mechanical properties, as suggested by the Italian building code. The effectiveness of the experimentally implemented and numerically simulated interventions are discussed in terms of strength enhancement and failure modes.