Thanks to its tolerance to drought, sorghum is a cereal crop that is extensively cultivated in the sub-Saharan region. Its good nutritional value makes it an interesting raw material for the food industry, although several anti-nutritional features pose a challenge to exploiting its full potential. In this study, we evaluated whether the process of germination may represent a way of improving the macro- and micro-molecular profile of sorghum, lowering the content of anti-nutritional factors, and promoting the synthesis of bioactive compounds. Germination for 48 and especially 72 h promoted the hydrolysis of starch and proteins, enhanced antioxidant activity, increased the content of polyphenols, mainly flavonols and flavanones, and promoted the conversion of γ- to α-isomers of tocopherols. At the same time, it significantly reduced the concentration of phytates and linoleic acid, enhancing pepsin activity and contributing to the inaugural examination of the impact of sprouted sorghum on digestive protease activity. These findings could help to promote the utilization of sprouted sorghum as a premium ingredient for food products, providing significant nutritional advantages.