Germination is a natural, simple, and economical process used to improve the quality of nutritional and technological grains. In this study, native and sprouted sorghum flours were characterized regarding their technological properties (particle size distribution, water, and oil absorption capacity, swelling power and solubility, microscopy of starch granules, and pasting and thermal properties). Nutritional and phytochemical characterization profiles, including free sugars, fatty acids, organic acids, tocopherols, and phenolic compounds, were explored through chromatographic methods. The antioxidant, anti-inflammatory, and cytotoxic activities of the respective hydroethanolic extracts were also evaluated. The results showed that the germination process caused significant changes in the flour composition and properties, causing reduced gelatinization temperature and retarded starch retrogradation; an increased content of free sugars and total organic acids; and a decreased content of tocopherols and phenolic compounds. In terms of bioactivity, the sprouted sorghum flour extract showed better lipid-peroxidation-inhibition capacity and none of the extracts revealed hepatotoxicity or nephrotoxicity, which are important results for the validation of the use of the flours for food purposes. Germination is an efficient and alternative method for grain modification that gives improved technological properties without chemical modification or genetic engineering.