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Background To investigate the value of Dickkopf-related protein 3 (DKK3) on aerobic glycolysis in pancreatic cancer cells, where DKK3-overexpression is used to determine its effects on CD4+ T cells. Methods The BxPC-3-DKK3 cell line was constructed, and peripheral blood mononuclear cell (PBMC) was prepared. After isolated the CD4+ T cells, the lactic acid, glucose uptake ability, cellular viability, proliferation, apoptosis, and markers were detected by PCR and western blot, and the concentrations of multiple cytokines were determined using the ELISA method. Results After co-culture with pancreatic cancer cells overexpressing DKK3, the glucose uptake markedly, proliferation enhanced and apoptosis inhibited in CD4+ T cells. The co-culture model also revealed that DKK3-overexpression promotes the activation and regulates the metabolism and function of CD4+ T cells. Conclusions DKK3 alters the metabolic microenvironment of pancreatic cancer cells and further facilitates the function of CD4+ T cells which suggesting that DKK3 may have a therapeutic potential in pancreatic cancer.