While piezoelectric sensing and energy-harvesting devices still largely rely on inorganic components, biocompatible and biodegradable piezoelectric materials, such as cellulose nanocrystals, might constitute optimal and sustainable building blocks for a variety of applications in electronics and transient implants. To this aim, however, effective methods are needed to position cellulose nanocrystals in large and high-performance architectures. Here, we report on scalable assemblies of cellulose nanocrystals in multilayered piezoelectric systems with exceptional response, for various application scopes. The submicrometer patterning with effective-flow topography and multilayer stacking promote piezoelectric performance. Record output power and pressure sensitivity in the gentle touch range are obtained in flexible, fully biodegradable systems with stable piezoelectric properties and demonstrated compatibility with different cell lines and implanted devices. These architectures offer new design principles for piezoelectric sustainable materials and for realizing an innovative class of practical components for mechanical energy harvesting and biologically relevant wearables and implants.