Bone is a hard connective tissue that undergoes a systematic renewal. This highly dynamic organ is made up of four different types of cells, however, bone formation is commonly attributed to osteoblasts and bone resorption to osteoclasts. Bone tissue formation occurs during embryonic development and in certain post-birth pathological conditions. The immune system could influence the functions of bone cells, and the crosstalk between hematopoietic, immune, and bone cells is known as osteoimmunology. Indeed, cytokines produced by immune cells, including TNF-α and IL-6, are critically implicated in bone pathogenesis. It is well established that diet plays an important role in bone health and function. Indeed, antioxidant nutraceuticals-rich diet, of which pearl millet is one, can be effective in treating osteoporosis. Pearl millet (PM) is an African native cereal that constitutes the staple food for African Sahel region inhabitants as well as for many peoples in rural regions in India. Pearl millet grains content in amino acids, minerals, and phytochemicals may contribute to promoting bone health and metabolism. Accordingly, in the current review, we discuss the putative effects of PM nutrients, with a focus on polyphenols, on bone metabolism and osteoimmunology. In the light of our previous studies and others from literature, we speculate that PM whole grains may be effective in the prevention and management of bone pathogenesis. ​Keywords: PM whole grains, polyphenols, osteoblasts, osteoclasts, osteoimmunology, TNF-α.