Pancreatic cancer is a highly lethal and aggressive tumor that affects the digestive tract, leading to high mortality and poor survival rates. At present, gemcitabine-based chemotherapy is widely used in the clinical treatment of pancreatic cancer. However, the efficacy of chemotherapy has significantly decreased with the emergence of clinical drug resistance. In order to meet its energy and biological materials, tumors always change its metabolic pathway, which is called tumor glucometabolic reprogramming. The abnormal enhancement of aerobic glycolysis is one of glucose metabolism reprogramming in pancreatic cancer cells. The glucose transporter proteins and key enzymes were participated in the processes and regulated chemotherapy resistance through different signal pathways. The purpose of this study was to summarize the relationship between drug resistance and glucose metabolism reprogramming in pancreatic cancer. The mechanisms and regulatory signaling pathways were also analyzed. Furthermore, the pre-clinical trials and drug development targeting the glycolysis metabolic pathways were summarized and analyzed.