Abstract: The integrated application of organic and inorganic fertilizers is a crucial measure for developing ecological and efficient agriculture. To investigate the effects of different organic water-soluble fertilizers combined with inorganic water-soluble fertilizer on foxtail millet growth and soil environment under drip irrigation, this study established six treatments: seaweed fertilizer + inorganic fertilizer (HNK), humic acid fertilizer + inorganic fertilizer (FNK), fish protein fertilizer + inorganic fertilizer (YNK), inorganic fertilizer alone (NK), irrigation only (WCK), and no fertilizer or irrigation (CK). The effects on millet yield, quality, water use efficiency (WUE), agronomic fertilizer use efficiency (FUE), soil nutrients, soil pH, and their correlations were analyzed. Results showed that all three organic-inorganic water-soluble fertilizer treatments significantly improved millet yield, quality, water/fertilizer use efficiency, and soil nutrient indicators compared to the NK treatment. The HNK treatment performed best in enhancing yield, productive panicles per plant, protein content, amylose-to-amylopectin ratio, WUE, and FUE, with yield and FUE showing substantial increases of 10.6%~11.5% and 25.8%~26.6%, respectively, over NK. The FNK and YNK treatments also effectively increased yield and WUE while improving grain quality, with yields significantly higher by 4.6%~6.5% compared to NK. The significant increase in productive panicles per plant was the primary reason for the yield improvement in organic-inorganic treatments versus NK. All three combined treatments significantly increased soil organic matter, total nitrogen, nitrate-N, available phosphorus, and available potassium content compared to NK, particularly showing a notable rise in soil organic matter within the two-year experiment. The HNK treatment most effectively boosted soil nitrate-N and available potassium, while FNK showed the greatest improvement in soil organic matter. Soil pH changes in the combined fertilizer treatments were more stable compared to NK, mitigating soil acidification. Correlation analysis revealed that soil available nutrients directly influenced millet yield, and soil organic matter content was significantly positively correlated with yield. Fertilization under drip irrigation had a greater impact on yield than irrigation alone. Grain protein content was significantly negatively correlated with amylose content, and gelatinization temperature was significantly positively correlated with amylose content. Overall, the combination of seaweed fertilizer and inorganic water-soluble fertilizer (HNK) is the optimal integrated application for enhancing millet yield, efficiency, and soil quality under drip irrigation conditions.