The use of nanotechnology in the piezoelectric industry conveys new concerns about the environmental toxicity related to lead based nanomaterials. Perovskite structured materials are extensively used as piezoelectrics, lead zirconate titanate (PZT) being the primary choice for sensors, actuators, etc., because of its powerful electromechanical conversion. However, during the life cycle of PZT piezoelectrics lead generally leaches into the environment over time, leading to human exposure and potential environmental hazard. Lead-free bismuth based-ferroelectric materials (BNT-BT) are promising substitutes due to their ability to provide all the piezoelectric attributes without leaching toxic material. Yet, little is known about the potential toxicity and interactions of these nanomaterials with biomolecules and their subsequent intracellular localization at the nanoscale. The aim of this study was to compare the biological impact and uptake of lead and bismuth-based piezoelectric nanoparticles in order to present a suitable substitute for the piezoelectric industry. Our results show that BNT-BT and PZT nanoparticles were internalized through the endolysosomal pathway following a first order kinetic, nanoparticles were localized in the lamellar bodies without inducing cell toxicity measured by mitochondrial activity and cell membrane integrity. Furthermore, BNT-BT nanoparticles were more stable as lead-based PZT released 20% more lead ions into cell culture media. Finally, we propose bismuth-based BNT-BT as a suitable candidate for commercial use as they avoid environmental leaching, imposing less risk during manufacturing and in occupational health, beside the high biocompatibility and similar physico-chemical properties.