The high incidence of kidney disease caused by various factors (such as COVID-19) has triggered an extreme desire for wearable artificial kidney (WAK). Nevertheless, the dialysate regeneration system in WAK presents a very low adsorption capacity of urea, and must rely on the help of urease and zirconium compounds, which make the device too complex and costly, thus limiting their application. In this study, we employ the adsorption activity of defect-rich MoS2 nanosheets with widened interlayer spacing (WDR-MoS2) for the elimination of three crucial uremic toxins (urea, creatinine, and uric acid). The high adsorption performances of WDR-MoS2 are owing to the presence of abundant S atoms between the two MoS2 sheets that can efficiently adsorb uremic toxins through the unique S–N bond. Furthermore, widening the layer spacing of MoS2 is similar to adjusting the aperture of a filter, which can not only speed up the transport of uremic toxins but also prevent the passage of large molecules (such as proteins). Thus, the WDR-MoS2 can neither affect cell viability nor produce hemolysis and coagulation in the blood. Finally, a home-made WDR-MoS2 fixed-bed system without urease and zirconium compounds is used to efficiently remove uremic toxins in the dialysate. WDR-MoS2 is expected to fundamentally solve the materials science challenges in WAK and provide a new design idea for the development of high-performance 2D material-based adsorbents.