<p>A porous double variable-valence FeCe nanozyme (pFeCezyme) was designed using hemoglobin as template and Fe-source. pFeCezyme exhibited excellent peroxidase (POD)-like activity due to the porous structure, maximized exposure of active sites, synergy of double variable-valence metals, and enhanced electron transfer between Fe and Ce. The POD-like activity can be quenched (off) by <span>l</span>-cysteine (<span>l</span>-Cys) and then restored (on) by adding of heavy metal ions (HMIs). The degree effect of “on–off” POD-like activity can be varied by changing pH conditions. Therefore, a three-channels pFeCezyme sensor array was established using pH values (pH = 4.0, 5.0, and 6.0) as sensing elements. Interestingly, pFeCezyme sensor array can generate distinct colorimetric fingerprints due to the different affinity ability between <span>l</span>-Cys and HMIs. The pFeCezyme sensor array was successfully applied to highly sensitive and high&#xa0;throughput discrimination of HMIs (Ag⁺, Hg²⁺, Cu²⁺, Cr⁶⁺, and Fe³⁺) even at low concentration of 0.1&#xa0;μM. Meanwhile, The&#xa0;pFeCezyme sensor array can rapidly distinguish binary and ternary mixed HMIs within 10&#xa0;min, and the HMIs and interfering substances can be well discriminated. Furthermore, the&#xa0;pFeCezyme sensor array could effectively distinguished HMIs in real samples with an excellent identification for unknow HMIs. This research provides a novel strategy for identifying a variety of HMIs, which exhibits a broad application prospect in HMIs monitoring.</p> Graphical Abstract <p></p>