Ionic liquids (ILs) play an important role in conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) based electronics and thermoelectrics through regulating morphology and electronic properties. Herein, the hole transport and interface electronic coupling properties of three kinds of IL ([BMIM]:[BF₄], [BuPhIM]:[BF₄], and [BnPhIM]:[BF₄]) mediated PEDOT systems have been researched via multiscale molecular mechanics simulations and quantum mechanics calculations, where the cations of the ILs feature gradually extended π-conjugation. It is indicated that [BnPhIM]:[BF₄] induces PEDOT to show more ordered π–π stacking than its counterparts, where the chains are oriented with face-to-face alignment. This is attributed to the larger evenness of the net charge distribution at the [BnPhIM]:[BF₄]-PEDOT interface. Consequently, the average mobility in [BnPhIM]:[BF₄]-PEDOT is 4.01 cm² V⁻¹ s⁻¹ and the instantaneous maximum reaches 17 cm² V⁻¹ s⁻¹, far surpassing its counterparts. Although the predicted PEDOT single crystal presents a well-ordered lamellar structure, the one-dimensional orientation causes hole tunneling along the nanowire-like direction, leading to its mobility lagging behind the [BnPhIM]:[BF₄] decorated system by one order of magnitude. On the other hand, the interface electronic coupling and doping efficiency in [BnPhIM]:[BF₄]-PEDOT is strengthened, confirming that improving the π-conjugation of the cation of the IL can enhance the mobility of PEDOT and interface electronic coupling synergistically. To improve the mobility further, a novel series of cations containing [BnPhIM-oOMe]⁺, [BnPhIM-mOMe]⁺, and [BnPhIM-pOMe]⁺ has been designed based on the outstanding properties of [BnPhIM]⁺. Combining the novel designed cations with [BF₄]⁻ and [B(CN)₄]⁻, it is observed that [BnPhIM-pOMe]:[B(CN)₄] causes PEDOT to assemble with well-ordered π–π stacking. Assessments rationalize that it could serve as a potential candidate for application in PEDOT-based electronics, since it shows similar interface electronic coupling and has a 35–43% improvement in PEDOT mobility compared to the excellent reference [BnPhIM]:[BF₄].