Neointimal hyperplasia is a known complication following aorta interventions. In this study, our hypothesis was that inhibiting phosphoglycerate kinase 1 (PGK1) could effectively reduce aortic neointimal hyperplasia in a rat model of abdominal aortic patch angioplasty. The role of the glycolytic pathway in patch angioplasty was analyzed by next-generation sequencing data, and the core role of PGK1 was found by differential gene analysis. The rats were allocated into two distinct groups: a control group that did not receive any supplementary treatment and a group treated with NG52, an inhibitor of PGK1, which was administered via a PLGA coating. Abdominal aortic patches were surgically implanted in the rats and subsequently harvested on the 14th day postimplantation for further analysis. Immunohistochemical analysis identified the presence of PGK1-positive cells within the neointima of the rat model subjected to abdominal aortic patch angioplasty. Importantly, the use of NG52 PLGA coating significantly decreased neointimal thickness (p < 0.0001). The mechanism of action of NG52 may involve the inhibition of TGFβ1 expression and the activation of the signaling pathway. Consequently, targeting the PGK1 pathway holds promise as a therapeutic strategy to mitigate aortic neointimal hyperplasia.