The two-dimensional (2D) twisted bilayer materials with van der Waals coupling have ignited great research interests, paving a new way to explore the emergent quantum phenomena by twist degree of freedom. Generally, with the decreasing of twist angle, the enhanced interlayer coupling will gradually flatten the low-energy bands and isolate them by two high-energy gaps at zero and full filling, respectively. Although the correlation and topological physics in the low-energy flat bands have been intensively studied, little information is available for these two emerging gaps. In this Letter, we predict a 2D second-order topological insulator (SOTI) for twisted bilayer graphene and twisted bilayer boron nitride in both zero and full filling gaps. Employing a tight-binding Hamiltonian based on first-principles calculations, three unique fingerprints of 2D SOTI are identified, that is, nonzero bulk topological index, gapped topological edge state, and in-gap topological corner state. Most remarkably, the 2D SOTI exists in a wide range of commensurate twist angles, which is robust to microscopic structure disorder and twist center, greatly facilitating the possible experimental measurement. Our results not only extend the higher-order band topology to massless and massive twisted moiré superlattice, but also demonstrate the importance of high-energy bands for fully understanding the nontrivial electronics.