Advances in neural electrode technologies can have a significant impact on both fundamental and applied neuroscience. Here, we report the development of flexible and biocompatible neural electrode arrays based on a nanopaper substrate. Nanopaper has important advantages with respect to polymers such as hydrophilicity and water wettability, which result in significantly enhanced biocompatibility, as confirmed by both in vitro viability assays and in vivo histological analysis. In addition, nanopaper exhibits high flexibility and good shape stability. Hence, nanopaper-based neural electrode arrays can conform to the convoluted cortical surface of a rat brain and allow stable multisite recording of epileptiform activity in vivo. Our results show that nanopaper-based electrode arrays represent promising candidates for the flexible and biocompatible recording of the neural activity.