Inspired by the nanointerface design of bio-derived structural materials, we design ductile and damage-tolerant carbon nanotube (CNT) fibers by utilizing conductive ionic silk fibroin (ISF) glue to regulate the CNT interface. The mechanical performance of the resulting CNT-ISF fibers is significantly improved, rendering an optimal combination of strength and toughness. Similar to other biological nanocomposites, the CNT-ISF fibers exhibit remarkable damage tolerance behavior due to confined CNT sliding and shearing during tensile fracture, supported by the synchrotron time-resolved small-angle scattering characterization and molecular dynamics simulations. Furthermore, the CNT-ISF fibers rendered an electric conductivity of 4.4 x 10(4) S m(-1), which is comparable to that of the pristine CNT fibers with the same dimensions. Moreover, the CNT-ISF fibers repeatedly exhibit a linear resistance response to tensile stress, which indicates that, instead of the conventional strain sensors, CNT-ISF fibers can be directly employed in stress sensors. Superior mechanical performance and high conductivity demonstrate the promising potential of CNT-ISF fibers in flexible and wearable devices, such as wearable sensors, smart textiles, artificial muscles and human-machine interfaces.