Inspired by the hydrolysis behaviors of skin cells, we exquisitely designed and synthesized a class of hydrolase mimics to develop an analytical method that can both identify and quantity antioxidant components in skin-whitening cosmetics, including ascorbic acid (AA) and its glycoside and phosphate derivatives. A series of ultra-thin Cu1-xMnxO2 or Fe1-yMnyO2 with rich acid-base pairs were prepared via chemical deposition and in-situ CuI/FeII self-assembly. H218O and D216O isotopic labeling studies and density function theory (DFT) calculations were adopted to analyze the cleaving sites of ascorbyl phosphate (AAL)/ascorbyl glucoside (AAP) and confirm that H2O was involved in the new bonds. In-situ DRIFT NH3-IR and −TPD further confirmed that the Fe- or Cu-substitution could increase the quantity and strength of Brønsted and Lewis acid sites. A cascade catalytic fluorescence sensor was designed for selective recognition or quantification of AA and its derivatives, which presents ultra-high-precision (≤2.5 %), stability, and selectivity in testing the target ingredients of five cosmetics from the market. Our nanozymes exhibit higher catalytic efficiency of 17.1 s−1 for AA, 8.42 s−1 for AAL, and 3.32 s−1 for AAP, which are 5.6 ∼ 32.8-fold higher than those of their mimic proteases. This work provides a controllable methodology to design hydrolytic nanozymes, which sheds light on biomimetic engineering and paves the way for breakthroughs in cosmetics industrial applications in the future.