Bioelectronics serves as an indispensable technology to directly interface with biological tissues for uncovering biological mechanism and applying health diagnosis and therapeutic interventions to the human body. Despite the considerable successes achieved on devices utilizing inorganic electronic materials, their high rigidity and limited stretchability lead to essential discomfort and even potential damage to the tissue, with their low biocompatibility posing significant obstacles for dealing with the foreign body response upon long-term implantation. On the contrary, conjugated polymer-based conductors/semiconductors show great promise for bio-integration due to their much higher ductility and chemical structures that closely resemble biomolecules. Among these, the redox-active semiconducting polymers (RASPs) possess the emerging class of conjugated polymer for their mixed ionic-electronic conduction capabilities, which enable highly efficient signal transduction and amplification by adopting the organic electrochemical transistor (OECT) configuration. To realize such processes at the tissue-electronic interface, however, relies on RASPs with biomimetic mechanical properties, and optimized mixed conduction properties. Unfortunately, these requirements are rarely met within the current category of RASPs. In my Ph.D. research, I focused on the development of RASPs with two major objectives, i.e., imparting tissue-like stretchability and softness on redox-active semiconducting polymers, and achieving high-efficiency auto-screening of high performance RASP films via a self-driving lab (SDL) for accelerating the material exploration and knowledge establishment process. First, I developed two highly stretchable RASPs, i.e., poly(2-(3,3′-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-[2,2′-bithiophen]-5)yl thiophene) (p(g2T-T)) and poly-[3,3′-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2′-bithiophene] (p(gT2)), that maintained consistent electrical performance even under 200% strain due to their ability to elongate and dissipate energy. Leveraging these materials, I fabricated intrinsically stretchable OECTs that demonstrated stable on-body electrophysiological signal recording and neuromorphic computing. Second, to address the significant modulus mismatch between RASPs and tissues, I proposed a simple and versatile solvent-exchange strategy for constructing RASP-embedded hydrogel composite, named hydrogel semiconductor (hydro-SC). Notably, the hydro-SC achieves the tissue-level modulus of 81 kPa, which is 3 orders of magnitude lower than the pristine RASP film, while maintaining the high charge-carrier mobility (0.61 cm2 V-1 s-1). In addition, the hydro-SC design also greatly enhances the biocompatibility of RASP for substantially alleviated immune response, and improves semiconductor porosity for more efficient photomodulation and maximized bioreceptor-analyte interaction. Third, to accelerate the development of high-performance RASP films that is mainly hindered by the sophisticated structure-property relationship, I developed a fully automated SDL together with an innovative human-machine collaboration mechanism. This optimized workflow resulted in a 150% improvement in performance compared to spin-coated films and led to the first discovery of a thermodynamically unfavorable polymorph in RASP films, which show strong correlations with volumetric capacitance (C*). All those outcomes were achieved with less than 70 experimental trials and only 10 samples for in-depth characterizations. In the final chapter, I provide summaries and future perspectives on the development of RASPs and OECT sensors for human integration, as well as the improvement of SDL towards the next generation.