Sprouting is an irreversible deterioration of potato quality, which not only causes loss in their commercial value but also produces harmful toxins. As a popular disinfectant, ClO2 can inhibit the sprouting of potato tubers. Using transcriptomic and metabolomic approaches to understand the repressive mechanism of ClO2 in potato sprouting is yet to be reported. Sequencing the transcriptome and metabolome of potatoes treated with ClO2 in this study revealed a total of 3,119 differentially expressed genes, with 1,247 and 1,872 genes showing down- and upregulated expression, respectively. The majority of the downregulated genes were associated with plant hormone signal transduction, whereas upregulated differential genes were associated primarily with biological processes, such as phenylpropanoid biosynthesis and the mitogen-activated protein kinase (MAPK) signaling pathway. Metabonomic assays identified a total of 932 metabolites, with 33 and 52 metabolites being down- and upregulated, respectively. Downregulated metabolites were mostly alkaloids, amino acids, and their derivatives, whereas upregulated metabolites were composed mainly of flavonoids and coumarins. Integrated transcriptomic and metabolomic analyses showed that many different metabolites were regulated by several different genes, forming a complex regulatory network. These results provide new insights for understanding the mechanism of ClO2-mediated repression of potato sprouting.