Levodopa is the most effective medication for treating Parkinson's disease (PD). However, because dose optimization is currently based on patients' report of symptoms, which are difficult for patients to describe, the management of PD is challenging. We report on a microneedle sensing platform for continuous minimally invasive orthogonal electrochemical monitoring of levodopa (L-Dopa). The new multimodal microneedle sensing platform relies on parallel simultaneous independent enzymatic-amperometric and nonenzymatic voltammetric detection of L-Dopa using different microneedles on the same sensor array patch. Such real-time orthogonal L-Dopa sensing offers a built-in redundancy and enhances the information content of the microneedle sensor arrays. This is accomplished by rapid detection of L-Dopa using square-wave voltammetry and chronoamperometry at unmodified and tyrosinase-modified carbon-paste microneedle electrodes, respectively. The new wearable microneedle sensor device displays an attractive analytical performance with the enzymatic and nonenzymatic L-Dopa microneedle sensors offering different dimensions of information while displaying high sensitivity (with a low detection limit), high selectivity in the presence of potential interferences, and good stability in artificial interstitial fluid (ISF). The attractive analytical performance and potential wearable applications of the microneedle sensor array have been demonstrated in a skin-mimicking phantom gel as well as upon penetration through mice skin. The design and attractive analytical performance of the new orthogonal wearable microneedle sensor array hold considerable promise for reliable, continuous, minimally invasive monitoring of L-Dopa in the ISF toward optimizing the dosing regimen of the drug and effective management of Parkinson disease. © 2019 American Chemical Society.