Leafy sweet potato is rich in caffeoylquinic acids (CQAs), including monoCQAs and diCQAs, which are important for plant resistance to environmental stresses. Knowledge about genes responsible for the accumulation of these CQAs is limited. However, the implication of glutathione S-transferase (GST) genes in the metabolism of plant secondary compounds has been reported. Yet, the mechanism of CQA-related GST proteins is not well understood. In this study, two sweet potato GST genes i.e., itb01g35330 (IbGSTTCHQD) and itb09g30700 (IbGSTT) were selected from our transcriptome database as they exhibited secondary metabolism functions based on gene ontology classification, and investigated for their association with the accumulation of CQAs. Sequence comparison of the IbGST coding regions amplified from EC16 and FS7-6 leafy sweetpotato varieties revealed some mutations at different sites in the amino acid sequences between the two varieties. Besides, the genes were highly expressed in EC16 compared to FS7-6, which corresponded to the amounts of CQAs in both varieties. The amplified sequences from EC16 were further transformed into Agrobacterium tumefaciens and subsequently introduced into Nicotiana benthamiana and Nicotiana tabacum for transient expression and transgenic transformation, respectively. Gene expression profiling in both experimental methods revealed significant increases of IbGST transcripts in transformed leaves, resulting in enhanced amount of monoCQAs compared to the wild types. However, no significant change was observed in the level of diCQAs. Moreover, the IbGSTs responded positively to salinity and oxidative stresses. Our findings suggested that IbGSTTCHQD and IbGSTT genes might be involved in the accumulation of monoCQAs in leafy sweet potato.