Bioelectronic implantable systems (BIS) targeting biomedical and clinical research should combine long-term performance and biointegration in vivo. Here, recent advances in novel encapsulations to protect flexible versions of such systems from the surrounding biological environment are reviewed, focusing on material strategies and synthesis techniques. Considerable effort is put on thin-film encapsulation (TFE), and specifically organic-inorganic multilayer architectures as a flexible and conformal alternative to conventional rigid cans. TFE is in direct contact with the biological medium and thus must exhibit not only biocompatibility, inertness, and hermeticity but also mechanical robustness, conformability, and compatibility with the manufacturing of microfabricated devices. Quantitative characterization methods of the barrier and mechanical performance of the TFE are reviewed with a particular emphasis on water-vapor transmission rate through electrical, optical, or electrochemical principles. The integrability and functionalization of TFE into functional bioelectronic interfaces are also discussed. TFE represents a must-have component for the next-generation bioelectronic implants with diagnostic or therapeutic functions in human healthcare and precision medicine.