In geomechanics and civil engineering, the distinct element method (DEM) is employed in a top-down manner to simulate problems involving mechanics of granular media. Because this particle-based method is well adapted to discontinuities, we propose here to adapt DEM at the mesoscale in order to simulate the mechanics of nanocrystalline structures. The modeling concept is based on the representation of crystalline nanograins as mesoscopic distinct elements. The elasticity, plasticity, and fracture processes occurring at the interfaces are captured with contact models of interaction between elements. Simulations that rely on the fitting of the peak stress, strain, and failure mode on the experimental testing of Au and CdS hollow nanocrystalline particles illustrate the promising potential of mesoscopic DEM for bridging the atomistic-scale simulations with experimental testing data.