An ideal microelectrode array (MEA) design should include materials and structures which exhibit biocompatibility, low electrode polarization, low impedance/noise, and structural durability. Here, the fabrication of MEAs with indium tin oxide (ITO) electrodes deposited with self-similar gold nanostructures (GNS) is described. We show that fern leaf fractal-like GNS deposited on ITO electrodes are conducive for neural cell attachment and viability while reducing the interfacial impedance more than two orders of magnitude at low frequencies (100-1000 Hz) versus bare ITO. GNS MEAs, with low interfacial impedance, allowed the detection of extracellular action potentials with excellent signal-to-noise ratios (SNR, 20.26 ± 2.14). Additionally, the modified electrodes demonstrated electrochemical and mechanical stability over 29 d in vitro.