Wearable microneedle array (MNA) based electrochemical sensors have gained increasing attention for their capability to analyze biomarkers in the interstitial fluid (ISF), enabling noninvasive, continuous monitoring of health parameters. However, challenges such as nonspecific adsorption of biomolecules on the sensor surfaces and the risk of infection at the microneedle penetration sites hinder their practical application. Herein, a wearable dual-layer microneedle patch was prepared to overcome these issues by integrating an antimicrobial microneedle layer with an antifouling sensing layer. The microneedle layer was prepared from polyvinyl alcohol, carboxylated nanocellulose, quaternary ammonium chitosan and carbon nanotubes, and it possessed antimicrobial and mechanical properties necessary for skin penetration, ISF collection and effective transmission to the sensing layer. The sensing layer was prepared from bacterial cellulose, epoxy propyl dimethyl dodecyl ammonium chloride, carbon nanotubes and gold nanoparticles, and it was capable of preventing biofouling and sensing uric acid (UA) in ISF. The wearable MNA based sensor exhibited a linear range of 0.5 μM - 2.5 μM and 9.6 μM - 2.15 mM for UA detection, with a limit of detection of 0.17 μM. Moreover, it was capable of accurately monitoring UA levels in ISF of mice without significant biofouling, as verified by the ELISA method. This innovative wearable sensor based on the MNA effectively balances the antifouling and antimicrobial functions, offering a reliable strategy for the assay of ISF, and making it a promising tool for personalized and decentralized health monitoring.