The deformation behavior of crystalline materials is influenced by microstructural features. To elucidate the deformation mechanisms of γ-TiAl, this study employs nanoindentation experiments and crystal plasticity finite element (CPFE) simulations to investigate the effects of crystal orientations and grain boundaries on the mechanical properties of γ-TiAl alloys. A crystal plasticity constitutive model was developed, and load-displacement curves, hardness, and Young"s modulus were obtained for both single grains and grain boundaries in γ-TiAl alloys. Based on the aforementioned model, this study systematically investigates the distribution patterns of surface morphology around the indentation sites of individual grains and grain boundaries. It also analyzes the cumulative shear strain distribution, slip system activation, and the interaction between grain boundaries and dislocation slip for various crystal orientations. The results indicate that the mechanical response and pileup behavior exhibit significant anisotropy due to the interplay between the indenter geometry, material slip systems, and cumulative shear strain distribution. Moreover, the interaction between grain boundaries and dislocation slip substantially alters dislocation distribution, thereby influencing material flow and playing a critical role in the mechanical response and plastic deformation of the material. These findings provide theoretical support for achieving high-quality surface machining of γ-TiAl alloys and other brittle materials.