Conventional electrodes are of significant challenges in acquiring bioelectric signals concerning a high signal-to-noise ratio (SNR), long-term and comfortable wear, low motional noise, etc. To resolve these issues, silk fibroin (SF) materials are adopted to create flexible microneedle array electrodes (FMNA-electrode) based on meso-engineering. The research approaches involve constructing flexible conductive electrodes from non-conductive and bristle-regenerated SF. By controlling the molecular interchain nucleation in the refolding process of unfolded regenerated SF molecules, this goal can be achieved. In this process, silver nanowires (Ag NWs) are adopted as meso-dopants to reconstruct the meso-electronic structure of SF films at the surface, while polyurethane (PU) is selected as molecular templates to facilitate the molecular nucleation in the refolding of SF molecules. This leads to the occurrence of SF-PU meso-hybridization, giving rise to more flexible meso-hybridized SF. The SF-PU FMNA-electrode demonstrates biocompatibility, comfort wearing, long-term monitoring capability, low motional noise, and a high SNR in the application of collecting ECG, EMG, and EOG signals. The outperformance of SF-PU FMNA-electrode is superior to both conventional wet and commercially available dry electrodes, paving the way for the next generation of flexible, skin-friendly, durable, and high-performance health monitoring devices and brain-machine interfaces.