Quantum dots (QD) are being evaluated as inorganic nanoparticles for both in vitro and in vivo optical imaging. They are also used as sensors or vehicles for targeted drug delivery combined with optical imaging. In this study, we demonstrated that glutathione coated Ag S QDs (GSH-Ag S QDs) act as a substrate analogue of glutathione-s transferase (GST) enzymes for the first time in the literature. The GSTs belong to a major group of detoxification enzymes involved in the detoxification metabolism responsible for the protection of cells against reactive oxygen species (ROS) or electrophiles. GST isozymes are impaired in the various diseases such as neurological diseases and cancer. We evaluated the interaction of GST-pi enzyme with GSH-Ag S QDs, which have never been studied in the literature before, using both fluorometric and spectrophotometric methods. Our data showed that GSH-Ag S QDs gave reaction with GST enzyme as a substrate analogue. In conclusion, our data may help to guide researchers for further development of sensing systems for GST activity which is impaired in various diseases including cancer. This article is protected by copyright. All rights reserved.