Diabetes, being the most widespread illness, poses a serious threat to global public health. It seems that inflammation plays a critical role in the pathophysiology of diabetes. This review aims to demonstrate a probable link between type 2 diabetes mellitus (T2DM) and chronic inflammation during its development. Additionally, the current review examined the bioactivity of natural flavones and the possible molecular mechanisms by which they influence diabetes and inflammation. While natural flavones possess remarkable anti-diabetic and anti-inflammatory bioactivities, their therapeutic use is limited by the low oral bioavailability. Several factors contribute to the low bioavailability, including poor water solubility, food interaction, and unsatisfied metabolic behaviors, while the diseases (diabetes, inflammation, etc.) causing even less bioavailability. Throughout the years, different strategies have been developed to boost flavones’ bioavailability, including structural alteration, biological transformation, and innovative drug delivery system design. This review addresses current advancements in improving the bioavailability of flavonoids in general, and flavones in particular. Clinical trials were also analyzed to provide insight into the potential application of flavonoids in diabetes and inflammatory therapies.