Abstract: Although Foxtail millet (Setaria italica P. Beauv.) is a relatively drought-tolerant C₄ model plant, drought is still an important factor restricting its growth, physiology, and production. To explore the physiological mechanism of drought-resistant millet mutants, we used wild-type ‘Yugu 28’ and its drought-resistant mutant (drm1-1) to explore their photosynthesis and drought tolerance characteristics when potted at the shooting stage and 10 d after flowering under drought-stressed conditions. Results showed that drm1-1 induced higher expression of photosynthesis-related genes, such as pepc (phosphoenolpyruvate carboxykinase), ppdk (pyruvate orthophosphate dikinase), and nadp-me (nadp-malic enzyme), and higher enzymatic activity of photosynthesis-related enzymes, which promoted greater photosynthesis under non-drought-stressed condition. Under drought-stress condition, the photosynthetic rate and chlorophyll fluorescence parameters of drm1-1 decreased significantly less than the wild-type plants under non-drought-stressed condition, showing a significant photosynthetic advantage. The leaf relative water content of drm1-1 also showed a significantly lower decrease than the wild-type plants under non-drought-stressed condition, and drm1-1 showed higher osmoregulation substance content and antioxidant enzyme activity than the wild-type plants, suggesting enhanced water holding capacity and drought resistance. Based on yield trait analysis, drm1-1 also exhibited outstanding yield advantages under drought stress condition.