Quantum dots (QDs) have been extensively investigated as fluorescent probes and are emerging as a new class of agents for biomedical imaging and diagnosis because of their broad absorption profiles, tunable emission wavelengths, and high photooxidation stability. QDs consist of an inorganic core surrounded by an organic shell. Normally, different types of biomolecules, such as amino acids, DNA, or peptides, are used for the organic shell to facilitate water solubility and biocompatibility of the QDs. However, because the core may contain toxic heavy metals (e.g., Cd, Hg, Pb, and Zn), the potential cytotoxicity of QDs has been a major impediment to their widespread application. It has therefore become critical to fully understand the interactions between QDs and living cells in order to develop nontoxic and biocompatible QDs for clinical use. Early studies have suggested that the release of core components, the generation of reactive oxygen species (ROS), and nonspecific binding to cellular membranes and intracellular proteins are the major mechanisms of the observed cytotoxic effects of QDs. Despite a significant surge in the number of investigations into the cytotoxicity of QDs, there is currently only limited knowledge about the cytological and physiological mediators of these effects. Interestingly, recent data have suggested that the induction of autophagy by certain sizes of QDs could play an important role in their toxic actions. Autophagy is a metabolic process involved in protein and organelle degradation and plays key roles in maintaining cellular homeostasis and contributing to cellular defense. It has been recognized as a third pathway of cell death, after apoptosis and necrosis, and is responsive to various physicopathological stimuli. Recent work has shown that small QDs (< 10 nm) rather than those with larger sizes (40–50 nm) induce autophagy in cultured cells. This size-dependent induction of autophagy has also been reported for other nanoparticles (NPs). However, all the above studies focused on the effects of type and size of the NPs, while other factors that may induce autophagy remain unexplored. Although many studies have demonstrated that surface modification of QDs with biomolecules endows them with various biological functionalities, the impact on living organisms of the chirality of the surface biomolecules has been largely neglected. Chirality is an important phenomenon in living systems and nearly all biological polymers must be homochiral to function. For example, all amino acids in proteins are “left-handed”, whereas all sugars in DNA and RNA are “right-handed”. Different chiral properties of biomolecules may determine their ability to interact with other biomolecules and thereby modulate a range of downstream processes. More recently, several attempts to develop chiral QDs with optical activities using different chiral stabilizers have been reported. Herein, the effects of QDs capped with different chiral forms of the tripeptide glutathione (GSH) on cytotoxicity and induction of autophagy were examined. Two different sizes of cadmium telluride (CdTe) QDs coated with either l-GSH (lGSH-QDs) or d-GSH (d-GSH-QDs) were found to show dose-dependent cytotoxicity and to significantly increase the levels of autophagic vacuoles. The activation of autophagy was chirality-dependent, with l-GSH-QDs being more effective than d-GSH-QDs. The ability of QDs to induce cell death was correlated with their ability to induce autophagy. This chirality-associated regulation of cellular metabolism and cytotoxicity highlights the important role of the conformation of the stabilizers, and has important implications for the design of novel QDs with enhanced optical properties and reduced or no toxicity. In this study, negatively charged water-soluble CdTe QDs were synthesized according to the Rogach–Weller method and coated with different chiral forms of GSH as stabilizers (Figure 1a). To clearly understand the chirality effect, two series of QDs were prepared. Group 1 comprised small-sized [*] Y. Li, Prof. Y. Zhao, Prof. G. Nie CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology 11 Beiyijie, Zhongguancun, Beijing 100190 (China) E-mail: niegj@nanoctr.cn