The conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) offers superior advantages in electronics due to its remarkable combination of high electrical conductivity, excellent biocompatibility, and mechanical flexibility, making it an ideal material among electronic skin, health monitoring, and energy harvesting and storage. Nevertheless, pristine PEDOT:PSS films exhibit limitations in terms of both low conductivity and stretchability; while, conventional processing techniques cannot enhance these properties simultaneously, facing the dilemma that highly conductive interconnected PEDOT:PSS domains are susceptible to tensile strain. Via modifying PEDOT:PSS with ionic liquids (ILs), not only a synergistic enhancement of the electrical and mechanical properties can be achieved but also the requirements for the printable bioelectronic are satisfied. In this comprehensive review, the task of providing a thorough examination of the mechanisms and applications of ILs as modifiers for PEDOT:PSS is undertaken. First, the theoretical mechanisms governing the interactions between ILs and PEDOT:PSS are discussed in detail. Then, the enhanced properties and the elucidation of the underlying mechanisms achieved through the incorporation of ILs are reviewed. Next, specific applications of ILs-modified PEDOT:PSS relevant to bioelectronic devices are presented. Last, there is a concise summary and a discussion regarding the opportunities and challenges in this exciting field.