Creating more exposed active sites on the metal-organic framework (MOF) surface is crucial for enhancing the recognition ability of MOF artificial receptors. Here, a copper-based MOF Cu(im)2 (im = imidazole) was utilized to act as an artificial receptor, inhibiting the activity of α-chymotrypsin. The shortest diazole ligand reduced the distance between regenerative copper sites, creating as many active sites as possible on the MOF unit surface. The amount of copper(ii) centers on the Cu(im)2 surface was calculated to be 4.96 × 106μm-2. Thus, Cu(im)2 showed exceedingly higher inhibition performance than other copper-based MOFs. The ChT activity was almost inhibited (88.8%) after the incubation with only 20 μg mL-1 Cu(im)2 for 10 min. The binding between ChT and Cu(im)2 was very fast with high affinity. Further results proved that Cu(im)2 inhibited the activity of ChT through electrostatic interactions and coordination interactions via the mixed inhibition mode. This strategy to use short ligands to create more active sites on the MOF surface provides a new direction to enhance the inhibition efficiency.