Introduction: Dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used oral antidiabetic agents that exert antihyperglycemic effects in type 2 diabetes mellitus (T2DM) without increased risk of weight gain or hypoglycemic events. The objective of this paper was to systematically review the latest evidence that was associated with the pharmacoeconomic evaluation of DPP-4i for the treatment of patients with T2DM. Areas covered: We conducted a systematic literature search of eligible articles published since inception up to March 2021 in Web of Science, MEDLINE (via PubMed), and ECONLIT. Fifty-four eligible articles were included in our review, in which DPP-4i were compared to metformin (4 studies), sulphonylurea (SU) (16 studies), alpha-glucosidase inhibitors (AGI) (3 studies), thiazolidinediones (TZD) (4 studies), other DPP-4i (3 studies), sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (10 studies), glucagon-like peptide 1 receptor agonist (GLP-1RA) (18 studies), insulin (5 studies), and other antidiabetic therapies (5 studies). Expert opinion: This study provided the updated evidence of systematic pharmacoeconomic evaluation associated with DPP-4i for the treatment of patients with T2DM. The evidence from the literature suggested that DPP-4i may be more cost-effective compared to SU and insulin as second-line therapy after metformin but not a cost-effective alternative compared to SGLPT-2i and GLP-1RA.