The interstitial fluid (ISF) is valuable for disease diagnosis due to its unique biomarkers. Microneedles (MNs) offer a painless method for ISF sampling, facilitating primary diagnostics. This study introduces a minimally invasive, biocompatible MN patch made from a swellable hydrogel of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which effectively extracts ISF. The hydrogel selectively permits small molecules like oxalate, a kidney disease biomarker, while blocking large biomolecules. The MN patch is integrated with a multilayer sensor via microfluidic channels, featuring cotton fiber, agarose, and Mn3[Fe(CN)6]2, alongside Fe3[Fe(CN)6]3 (AGH-CP/MnFeCN/FeFeCN). These nanozymes exhibit oxidase-like activity, reacting with 3,3′,5,5′-tetramethylbenzidine (TMB) to indicate oxalate levels through a color change from green (no oxalate) to light or dark blue, based on concentration. The designed sensor demonstrates high performance with a detection limit of 0.897 μM and an RSD of 1.22 %, enabling accurate quantification via smartphone image analysis as readout platforms for more accessibility and user-friendliness which helps to reach personalized healthcare goals. This integration facilitates real-time, remote, precise disease detection, biochemical analysis and forsooth miniaturization, leading to the development of portable, flexible, and wearable sensors. The MN patch and integrated sensor show excellent stability, selectivity, sensitivity, reliability, and long-term durability. This minimally invasive sensing system, designed for wristband integration, opens new avenues for precision point-of-care monitoring, enhancing personal healthcare.