A metal-organic framework (MOF)-encapsulated nanozyme has been developed to detect L-cysteine (L-Cys) through a facile colorimetric sensing method in this study. This nanozyme was prepared by encapsulating Fmoc-histidine (FH) and hemin within ZIF-8 (FH/hemin@ZIF-8) and exhibited significantly enhanced catalytic activity and great stability because of its unique structure. FH/hemin@ZIF-8 oxidized colorless 3,3',5,5'-tetramethylbenzidine (TMB) to a distinct blue color with the assistance of H2O2. However, after the addition of L-Cys, this oxidation process was inhibited, resulting in the solution fading from blue to colorless. This change can be observed by the naked eyes and quantitatively analyzed using a UV-vis spectrophotometer. Additionally, this system demonstrated excellent resistance to interference and exceptional selectivity. In addition, this system showed a low detection limit of 23.1 nm (S/N = 3). Consequently, it is believed that the strategy of encapsulating biomimetic nanozymes within MOFs holds significant potential for applications in bioanalysis and the early diagnosis of L-Cys.