This paper describes the first implementation of an array of two-dimensional (2D) layered conductive metal-organic frameworks (MOFs) as drop-casted film electrodes that facilitate voltammetric detection of redox active neurochemicals in a multianalyte solution. The device configuration comprises a glassy carbon electrode modified with a film of conductive MOF (M3HXTP2; M = Ni, Cu; and X = NH, 2,3,6,7,10,11-hexaiminotriphenylene (HITP) or O, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP)). The utility of 2D MOFs in voltammetric sensing is measured by the detection of ascorbic acid (AA), dopamine (DA), uric acid (UA), and serotonin (5-HT) in 0.1 M PBS (pH = 7.4). In particular, Ni3HHTP2 MOFs demonstrated nanomolar detection limits of 63 ± 11 nM for DA and 40 ± 17 nM for 5-HT through a wide concentration range (40 nM-200 μM). The applicability in biologically relevant detection was further demonstrated in simulated urine using Ni3HHTP2 MOFs for the detection of 5-HT with a nanomolar detection limit of 63 ± 11 nM for 5-HT through a wide concentration range (63 nM-200 μM) in the presence of a constant background of DA. The implementation of conductive MOFs in voltammetric detection holds promise for further development of highly modular, sensitive, selective, and stable electroanalytical devices.