Wearable metabolite sensors are often limited by easily denaturable enzymes that only allow short-duration monitoring. Although encapsulating enzymes in metal–organic frameworks (MOFs) shows promise of long-term enzyme protection, it is typically accompanied by significantly decreased activity due to increased diffusion barrier, steric hindrance for enzyme-substrate binding, and poor enzyme-electronic interface. Herein, the co-encapsulation of enzymes and ultrasmall arginine-derived carbon dots (Argdot) into a mesoporous Zeolitic Imidazolate Framework-8 (mZIF-8) matrix and the enhancement effect of Argdot on enzyme stability and activity, which consequently improves the electrochemical sensor's long-term sensitivity are investigated. Specifically, the glucose oxidase (GOx)-Argdot@mZIF-8 nanocomposite consistently exhibits 40% higher electrochemical sensitivity compared to control GOx@mZIF-8, an improvement similarly demonstrated with another model enzyme lactate oxidase (LOx). Furthermore, GOx-Argdot@mZIF-8 displays excellent stability, retaining 100% of initial sensitivity over 30 days of repeated testing at 37 °C. A touch-based glucose sensor prototype is demonstrated as an excellent reusable sensor to monitor finger-tip sweat glucose levels over one month at room temperature. This enzyme encapsulation strategy is not only useful for developing reusable sweat sensors with long-term monitoring capability, but also promising to expand the industry use of enzymes under harsh conditions.