Following implantation, neuroelectrode functionality is susceptible to deterioration via reactive host cell response and glial scar‐induced encapsulation. Within the neuroengineering community, there is a consensus that the induction of selective adhesion and regulated cellular interaction at the tissue–electrode interface can significantly enhance device interfacing and functionality in vivo. In particular, topographical modification holds promise for the development of functionalized neural interfaces to mediate initial cell adhesion and the subsequent evolution of gliosis, minimizing the onset of a proinflammatory glial phenotype, to provide long‐term stability. Herein, a low‐temperature microimprint‐lithography technique for the development of micro‐topographically functionalized neuroelectrode interfaces in electrodeposited poly(3,4‐ethylenedioxythiophene):p‐toluene sulfonate (PEDOT:PTS) is described and assessed in vitro. Platinum (Pt) microelectrodes are subjected to electrodeposition of a PEDOT:PTS microcoating, which is subsequently topographically functionalized with an ordered array of micropits, inducing a significant reduction in electrode electrical impedance and an increase in charge storage capacity. Furthermore, topographically functionalized electrodes reduce the adhesion of reactive astrocytes in vitro, evident from morphological changes in cell area, focal adhesion formation, and the synthesis of proinflammatory cytokines and chemokine factors. This study contributes to the understanding of gliosis in complex primary mixed cell cultures, and describes the role of micro‐topographically modified neural interfaces in the development of stable microelectrode interfaces.