Emerging evidence suggests that sustained diabetes-associated factors such as inflammation, hyperinsulinemia, and hyperglycemia are major contributors to aberrant cell proliferation and subsequent neoplastic transformation. Epidemiological studies have also highlighted that diabetes promoting a sedentary lifestyle, with or without the direct involvement of insulin, is frequently linked to cancer. However, our knowledge regarding the molecular mechanisms that correlate hyperglycemia to oncogenic transformations remains limited. In this regard, a recent study has proved that hyperglycemia inactivates AMPK, which results in the destabilization of the TET2 and its tumour-suppressive role ultimately predisposing diabetes mellitus patients to cancer. To the management of hyperglycemia associated with oncogenesis, we need to explore a reverse pharmacology-based ethnopharmacological approach. Botanical-derived natural products are structurally and functionally more diverse with fewer or no side effects on humans. The present review discusses the molecular link between hyperglycemia and cancer progression with the effect of natural products as therapeutic agents on the hyperglycemia-cancer associated signalling pathway.