【Objective】To establish scientifically grounded, synergistic regulatory approaches for the comprehensive mitigation of the persistent challenge of saline–alkali soil degradation in cotton-growing systems, this study conducted a controlled field experiment during the 2024 cotton season on moderately saline–alkali soils in Manas County, Xinjiang. The objective was to elucidate how the integrated application of poly-γ-glutamic acid (γ-PGA) and regulated irrigation influences soil biochemical processes, cotton physiological performance, yield formation, and fibre quality under field conditions.【Method】A two-factor randomized block design was established, involving three γ-PGA rates (F1: 7.5 kg·hm-2; F2: 15 kg·hm-2; F3: 22.5 kg·hm-2) and two irrigation quotas (W1: 4 000 m3·hm?2; W2: 4 500 m3·hm?2). Comprehensive measurements included soil physicochemical indices (Electrical conductivity (EC) -based salinity and pH variations across growth stages), key enzymatic activities (polyphenol oxidase, catalase, urease, sucrase), root morphological traits (length, diameter, biomass ratios), organ-specific dry matter accumulation, and yield and fibre parameters (boll number, lint percentage, composite quality index).【Result】Compared with F1 and F2, the F3 treatment effectively suppressed peak soil salinity and pH, concurrently elevating enzymatic activity, particularly urease, which increased by 30.13%-35.22 %. Nevertheless, the response plateaued beyond the F3 level, suggesting diminishing returns under higher γ-PGA concentrations. Enhanced enzymatic activity and improved rhizosphere conditions promoted root proliferation and biomass accumulation, resulting in a moderate but statistically significant yield increase (3.02%–27.96 %). Likewise, a higher irrigation quota (W2) alleviated surface salt accumulation and improved enzyme activities by 9.16%-48.33%, although excessive irrigation risked secondary salinization through capillary rise and nutrient leaching. Also, multivariate analyses (Principal component analysis and Pearson correlation) revealed a strong positive correlation (P < 0.05) between enzyme activity and yield traits. At the same time, soil salinity and alkalinity showed negative correlations with fibre quality indices, emphasizing the trade-off between osmotic stress alleviation and fibre maturation under saline conditions.【Conclusion】The combined application of 22.5 kg·hm?2 γ-PGA with 4 500 m3·hm?2 irrigation proved the most efficient configuration within the tested range, primarily by ameliorating the rhizosphere microenvironment (lower EC/pH and enhanced enzymatic turnover) and optimizing photosynthate allocation to reproductive organs. However, the overall improvement remains conditional on soil salinity thresholds, long-term stability, and economic feasibility. Thus, while the integrated γ-PGA–irrigation strategy significantly enhances cotton yield and fibre quality in saline–alkali soils, its scalability and sustainability under variable climatic and hydrological regimes warrant further investigation.