Ammonia is a neurotoxin that can lead to significant and permanent neurological impairment. The accumulation of ammonia in the blood of patients with liver failure can cause life-threatening hepatic encephalopathy. However, until now, there has been a lack of efficient, safe, and specific adsorbents to remove ammonia from the blood of patients with liver failure. In this study, chitin/zeolite composite nanofibrous microspheres (CZ) were prepared and evaluated as safe, efficient, and specific blood ammonia sorbents to remove ammonia from hyperammonemia plasma for the treatment of hyperammonemia. The CZ microspheres were characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, physical adsorption of N2, scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. CZ consists of intertwined nanofibrous network microspheres constructed from chitin nanofibers and embedded zeolite. In the in vitro adsorption experiment, CZ exhibited rapid and good affinity for ammonia in both aqueous solution and hyperammonemia plasma. The adsorption capacity of CZ2 in aqueous solution was 17.673 mg/g, which is similar to that of zeolite. The level of blood ammonia in the hyperammonemia plasma decreased from 650 to 386 μmol/L after adsorption by CZ2. In addition, CZ has been demonstrated to have good compatibility with cells and blood components (such as erythrocytes, clotting factors, and proteins), exhibiting good biocompatibility and blood compatibility. All these meet the necessary requirements for the clinical use of blood ammonia adsorbents for blood purification. Therefore, CZ has potential applications in the ammonia-induced treatment of complications.