Sorghum and pearl millet are grain crops that can grow in semi-arid climates, with nutritional and bioactive properties superior to those of major cereals such as rice, wheat, and maize. However, these properties vary a lot, depending on the genetic factors, growing conditions, and place of cultivation. Four sorghum and two pearl millet grains cultivars grown in the Far-North region of Cameroon were screened for their chemical composition and antioxidant profile. The proximate and mineral analyses were performed using AOAC standard methods. The antioxidant profile was assayed spectrophotometrically and details on the phenolic compounds were investigated using HPLC. The pearl millet cultivars, especially mouri, showed higher contents of proteins, lipids, ash, calcium, copper, iron, and zinc. The red sorghum specifically exhibited the greatest amounts of total polyphenols (82.22 mg GAE/g DE), total flavonoids (23.82 mg CE/g DE), and total 3-deoxyanthocyanidin (9.06 mg/g DE). The most abundant phenolic compound was gallic acid, while the most frequent were chlorogenic and ferulic acids. The maximum antioxidant activity against DPPH was observed in yellow-pale sorghum (87.71%), followed by red sorghum (81.15%). Among the studied varieties of cereals, mouri pearl millet and red sorghum were the best sources of nutrients and bioactive compounds, respectively. Their consumption should be encouraged to tackle nutrient deficiencies and non-communicable diseases within local populations.