A manganese-based metal–organic framework (Mn-BTC) with oxidase-like activity was successfully synthesized via a solvothermal method using divalent manganese ions (Mn2+) as metal nodes and trimesic acid (H3BTC) as the organic ligand. It can catalyze the conversion of dissolved oxygen into reactive oxygen species (ROS), thereby oxidizing the colorless substrate 3,3′,5,5′-tetramethylbenzidine (TMB) to the blue product oxidized TMB (oxTMB). In the presence of nitrite ions (NO2?), NO2? undergoes a diazotization reaction with oxTMB to form a yellow diazo compound, leading to a decrease in absorbance at 652 nm and the appearance of a new absorption peak at 450 nm, accompanied by a gradual color change of the solution from blue to yellow. Based on this phenomenon, a highly sensitive and selective ratiometric colorimetric sensing method for NO2? was constructed, with a detection range of 50–250 μM and a limit of detection of 1.90 μM, and successfully applied to the determination of NO2? in pickle samples.