Quantum Dots (QDs) are becoming more prevalent in products used in our daily lives, such as TVs and laptops, due to their unique and tunable optical properties. The possibility of using QDs as fluorescent probes in applications, such as medical imaging, has been a topic of interest for some time, but their potential toxicity and long-term effects on the environment are not well understood. In the present study, we investigated the effects of yellow CdSe/ZnS-QDs on Saccharomyces cerevisiae. We utilized growth assays, RNA-seq, reactive oxygen species (ROS) detection assays, and cell wall stability experiments to investigate the potential toxic effects of CdSe/ZnS-QDs. We found CdSe/ZnS-QDs had no negative effects on cell viability; however, cell wall-compromised cells showed more sensitivity in the presence of 10 µg/mL CdSe/ZnS-QDs compared to non-treated cells. In CdSe/ZnS-treated and non-treated cells, no significant change in superoxide was detected, but according to our transcriptomic analysis, thousands of genes in CdSe/ZnS-treated cells became differentially expressed. Four significantly differentiated genes found, including FAF1, SDA1, DAN1, and TIR1, were validated by consistent results with RT-qPCR assays. Our transcriptome analysis led us to conclude that exposure of CdSe/ZnS-QDs on yeast significantly affected genes implicated in multiple cellular processes.