Two unique immunosensors made of aluminum-based metal-organic frameworks (MOFs), namely, 515- and 516-MOFs, with 4,4',4''-nitrilotribenzoic acid (H3NTB) were successfully obtained to efficiently assess food safety. The as-prepared 515- and 516-MOFs exhibited superior thermal and physicochemical stability, high electrochemical activity, and good biocompatibility. Among these immunosensors, 516-MOF showed a preferable biosensing ability toward analytes determined by electrochemical techniques. The developed 516-MOF-based electrochemical biosensor not only demonstrated high sensitivity with low detection limits of 0.70 and 0.40pgmL−1 toward vomitoxin and salbutamol, respectively, but also showed good selectivity in the presence of other interferences. Therefore, with the advantages of high sensitivity, good selectivity, and simple operation, this new strategy is believed to exhibit great potential for simple and convenient detection of poisonous and harmful residues in food. •Two high-stable Al-MOF-based immunosensors were constructed.•High sensitivity and selectivity of the developed biosensor.•Ultra-sensitively detecting poisonous and harmful residues in food.