Song Dynasty tilestones are one type of ancient Chinese building materials. Studying their mechanical properties is of great significance for the design and development of restoration materials. It is a challenge to sample and perform traditional tests (ϕ50mm × 100mm) for the tilestone cultural relics. In this work, a combination of nanoindentation techniques and the homogenization calculation method based on the Mori–Tanaka model were used to determine the mechanical parameters of Song Dynasty tilestones. The study process involved several steps: (1) Using X-ray diffraction and scanning electron microscopy to examine the surface morphology and mineral composition of the tilestones. (2) Determining the mechanical parameters (i.e., the elastic modulus, hardness and fracture toughness) through nanoindentation tests. (3) Upgrading mechanical parameters from micro to meso-scale using the Mori–Tanaka model and comparing these with uniaxial compression test results. The result shows that the red tilestones and green tilestone are mainly composed of quartz, feldspar and mica. The average elastic modulus of the red tilestones and the green tilestones are 29.47 GPa and 30.21 GPa, respectively. Compared with the parameter result obtained by upscaling, the deviation rates of the red tilestones and green tilestones are 10.3% and 9.6%, respectively, which proves that the test method is reliable. The nanoindentation test and homogenization approach in this work provide the robust theoretical and practical basis for evaluating the mechanical strength of Song Dynasty tilestones.