Biofuel cells (BFCs)-based self-powered biosensors suffer from the limited stability of bioenzymes. Meanwhile, the poor performance of self-powered biosensors affects the sensitivity of biosensing, thus, it is significant and challenging to improve their stability and sensitivity. Researchers from Qingdao Agricultural University constructed a BFC-based self-powered biosensor with simultaneously enhanced stability and sensitivity utilizing dual metal-organic frameworks (MOFs) as the carriers of the bioenzyme and the electroactive probe, respectively. Anodic enzyme, glucose dehydrogenase (GDH), was encapsulated in zeolitic imidazolate framework-8 (ZIF-8) to form GDH@ZIF-8 composites, enhancing the catalytic activity and stability of GDH. Meanwhile, another zirconium metal-organic frameworks (UiO-66-NH2) loaded with electroactive molecules (K3[Fe(CN)6]) served as nano-enrichment carriers and improved the capability of the cathode to accept electrons from the anode, further improving the sensitivity of the as-proposed biosensor. Herein, the “signal-on” BFC-based self-powered biosensing of exosomes, the model analyte, with excellent stability and outstanding sensitivity was realized with the assistance of dual MOFs, and the detection limit was down to 300 particles mL−1 (based on 3s/k), which was superior to those previously reported in literatures. Furthermore, the developed protocol was capable of detecting exosomes derived from cancer cells in complex biological samples. Overall, in this work the enhancement of both stability and sensitivity has been achieved by utilizing two types of MOFs, which laid the foundation for expanding the applications of BFC-based self-powered biosensors.