In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 μg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R2 = 0.9889), and the LOD was 0.073 μg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.