Sorghum and millets are drought-tolerant cereals grown mainly in semi-arid regions of the world. They are important sources of food for many communities in these regions. Sorghum and millets are also known to be sources of phytochemical and bioactive compounds with potential health-promoting properties. These compounds include phenolics (phenolic acids, flavonoids, and tannins), phytosterols, policosanols, and bioactive peptides. There is a gradual accumulation of evidence in the scientific literature that these bioactive compounds have potential to combat diet-related noncommunicable diseases such as cancer, cardiovascular disease, and diabetes, among others. The bioavailability of phytochemicals such as phenolic compounds specifically in sorghum and millets and their foods has not been studied. However, there are literature reports that show that phenolic compounds can be absorbed within the gut although they are largely metabolized and excreted. Various in vitro, ex vivo, and in vivo methods have been used to investigate and demonstrate the health-promoting attributes of sorghum and millets that are linked to their bioactive compounds. There is a need for more in vivo animal and human intervention research studies on the fate and bioavailability of bioactive compounds in sorghum and millets and their foods and how these may be linked to combating diet-related noncommunicable diseases.