AbstractNumerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the reactive oxygen species (ROS)/reactive nitrogen species (RNS) reactions, particularly quasi‐stable oxidized products, have been much less explored. In this report, we observed that half‐curcumins could generate chemiluminescence (CL). In contrast to other chemiluminescence scaffolds, the distinguishing feature of a half‐curcumin is the formation of a carbanion intermediate of its acetylacetone moiety, opening unique avenues for applications. In this study, we designed a series of half‐curcumins CRANAD‐Xs and found that CRANAD‐164 could be used to detect quasi‐stable oxidized proteins (QSOP) in vivo and in patient serum samples. We illustrated that CRANAD‐164 could be used to monitor the responses of taurine, an amino acid with newly reported anti‐aging capacity, in an inflammatory mouse model. Remarkably, we further demonstrated that the QSOP levels were much higher in the disease serum samples, including Alzheimer's disease (AD), compared to the samples from healthy controls. Moreover, our results revealed that the sera chemiluminescence intensities were higher in aged healthy controls compared to young healthy subjects, suggesting that CRANAD‐164 can be used to monitor the increase of QSOP during aging.