Neural interface is a powerful tool to control the varying neuron activities in the brain, where the performance can directly affect the quality of recording neural signals and the reliability of in vivo connection between the brain and external equipment. Recent advances in bioelectronic innovation have provided promising pathways to fabricate flexible electrodes by integrating electrodes on bioactive polymer substrates. These bioactive polymer-based electrodes can enable the conformal contact with irregular tissue and result in low inflammation when compared to conventional rigid inorganic electrodes. In this review, we focus on the use of silk fibroin and cellulose biopolymers as well as certain synthetic polymers to offer the desired flexibility for constructing electrode substrates for a conformal neural interface. First, the development of a neural interface is reviewed, and the signal recording methods and tissue response features of the implanted electrodes are discussed in terms of biocompatibility and flexibility of corresponding neural interfaces. Following this, the material selection, structure design and integration of conformal neural interfaces accompanied by their effective applications are described. Finally, we offer our perspectives on the evolution of desired bioactive polymer-enabled neural interfaces, regarding the biocompatibility, electrical properties and mechanical softness.