The flowering stage is a critical period for water sensitivity and quality formation of broomcorn millets. However, the effects and mechanisms of drought stress on the quality formation of broomcorn millets are not clear. We used the drought-resistant variety Hequ red millet (H) and the drought-sensitive variety Yanshu No. 10 (Y) were used as materials for drought stress treatment during the flowering stage, metabolomics and physiological methods were used to study the differences in protein, starch, amino acids, medium and medium-long chain fatty acids, and their response characteristics to drought in broomcorn millet. The results showed that different genotypes of broomcorn millets exhibited different response mechanisms in the face of drought stress. In Hequ red millet, drought stress significantly increased the contents of amylopectin (2.57%), pyridoxine (31.89%), and anthocyanin, and significantly decreased the contents of water-soluble protein (5.82%), glutelin (10.07%), thiamine (14.95%) and nicotinamide (23.01%). In Yanshu No. 10, drought significantly decreased amylose by 6.05%, and significantly increased riboflavin and nicotinamide contents by 21.11% and 32.59%. Correlation analysis showed that total starch and amylose were highly significantly positively correlated with methyl palmitate; negatively correlated with amylopectin, vitamins, proteins, free amino acids, and medium-long chain fatty acids; and amylopectin was significantly positively correlated with water-soluble protein, riboflavin, and pyridoxine. Water-soluble protein and glutelin were significantly positively correlated with most free amino acids, medium-long chain fatty acids, and nicotinamide. Thiamine showed significant positive correlation with nicotinamide and significant negative correlation with pyridoxine. Riboflavin was significantly positively correlated with nicotinamide, pyridoxine, and water-soluble protein, and pyridoxine was significantly positively correlated with water-soluble protein. Hequ red millet transforms into amylopectin by consuming water-soluble protein and glutelin, and improves drought resistance by accumulating pyridoxine, and changes its physicochemical properties by decreasing the content of amylose and protein and elevating the content of amylopectin. Yanshu No. 10 resisted drought by catabolizing lipids to produce fatty acids and by consuming amylose for conversion into other metabolites. The present study helps to understand the response of the nutritional quality of millets to drought stress at the flowering stage and provides a theoretical basis for the selection and breeding of superior varieties of millets and drought resistance research.