Whole-grain sorghum foods may elicit health-promoting effects when consumed regularly in the diet. This review discusses key functional sorghum grain constituents, including dietary fiber, slowly digestible and resistant starches, lipids, and phytochemicals and their effects on metabolic processes that are associated with the development of chronic diseases, such as heart disease and diabetes. Currently, the range of sorghum food products available to consumers is limited globally, hindering the potential consumer benefits. A collaborative effort to innovate new product developments is therefore needed, with a focus on processing methods that help to retain the grain's favorable nutritive, health-enhancing, and sensory attributes. Evidence for sorghum's purported health effects, together with evidence of impacts of processing on different sorghum foods, are presented in this review to fully elucidate the potential of sorghum grain to confer health benefits to humans.