Hydrogen peroxide, phenols, amines, aldehydes, and other substances can easily damage intracellular biomacromolecules. Although natural peroxidases can convert these harmful substances into benign ones, the high costs, poor stabilities, and stringent application conditions associated with these enzymes necessitate the exploration of artificial mimics. In this study, Ce-doped MIL-101(Fe)-NH2 and MIL-101(Fe)-NO2 were synthesized with varying compositions via a solvothermal method. The materials were characterized, and their peroxidase-like activities were compared under optimal conditions after optimizing the reaction conditions. Previous studies have suggested that the undoped MIL-101(Fe)-NO2 exhibits a superior peroxidase-like activity to that of the undoped MIL-101(Fe)-NH2. Our experimental results demonstrated the opposite trend, in stark contrast to previous findings. Based on these experiments, the fundamental processes were examined through computational methods. The Ce-doped Fe metal-organic framework exhibited lower detection limits and wider detection ranges for hydrogen peroxide and ascorbic acid when used as a sensitive colorimetric sensor.