Urea removal is one of the biggest challenges in dialysate regeneration in Wearable Artificial Kidney (WAK) devices. In this work, a new Mixed Matrix Membrane (MMM) is developed for urea removal in WAK applications. The MMM consists of polystyrene-based ninhydrin particles within a polyethersulfone/polyvinylpyrrolidone polymer blend matrix. The MMM is prepared via dry-wet spinning technique and characterized in terms of its morphology via electron microscopy and clean water permeance. Urea removal is studied both in static and in dynamic conditions. Thanks to the good dispersion of small size ninhydrin particles (size < 63 µm), the MMM removed under static conditions, at 70 °C, 2.1 ± 0.1 mmol of urea per grams of particles at 24 h, while urea removal by the particles in suspension reached 1.7 ± 0.1 mmol/g under the same conditions. Importantly, in continuous recirculation experiments, performed at 70 °C using a laboratory scale module, the MMM removed 3.4 ± 0.3 mmol of urea per grams of particles, in 4 h, due to the high particle accessibility by urea within the membrane. Based on these results it is estimated that only 215 g of MMM are needed for removing the daily produced urea from spent dialysate (400 mmol) making MMM suitable for application to WAK, where miniaturization and lightweight are required.