Herein, a paper-based electrochemical sensor based on PtNP/COFTFPB−DHzDS@rGO was developed for the sensitive detection of furazolidone. A cluster-like covalent organic framework (COFTFPB−DHzDS) was successfully grown on the surface of amino-functional reduced graphene oxide (rGO-NH2) to avoid serious self-aggregation, which was further loaded with platinum nanoparticles (PtNPs) with high catalytic activity as nanozyme to obtain PtNP/COFTFPB−DHzDS@rGO nanocomposites. The morphology of PtNP/COFTFPB−DHzDS@rGO nanocomposites was characterized, and the results showed that the smooth rGO surface became extremely rough after the modification of COFTFPB−DHzDS. Meanwhile, ultra-small PtNPs with sizes of around 1 nm were precisely anchored on COFTFPB−DHzDS to maintain their excellent catalytic activity. The conventional electrodes were used to detect furazolidone and showed a detection limit as low as 5 nM and a linear range from 15 nM to 110 μM. In contrast, the detection limit for the paper-based electrode was 0.23 μM, and the linear range was 0.69–110 μM. The results showed that the paper-based electrode can be used to detect furazolidone. This sensor is a potential candidate for the detection of furazolidone residue in human serum and fish samples.