Recent advances in bioelectronics, such as skin-mounted electroencephalography sensors, multi-channel neural probes, and closed-loop deep brain stimulators, have enabled electrophysiological brain activities to be both monitored and modulated. Despite this remarkable progress, major challenges remain, which stem from the inherent mechanical, chemical, and electrical differences that exist between brain tissues and bioelectronics. New approaches are therefore required to address these mismatches between biotic and abiotic systems. Here, we review recent technological advances that minimize such mismatches by using unconventional soft materials, such as silicon/metal nanowires, functionalized hydrogels, and stretchable conductive nano composites, as well as customized fabrication processes and novel device designs. The resulting novel, soft bioelectronic devices provide new opportunities for brain research and clinical neuroengineering.