Abstract: To enhance the antioxidant activity and flavor characteristics of wheat bran, this study employed in vitro antioxidant evaluation methods to isolate and screen six lactic acid bacteria strains from fermented foods that were capable of improving the antioxidant capacity of wheat bran. These strains were then co-fermented with a laboratory-preserved S. cerevisiae HNGD-JZ to identify the optimal microbial combination. The volatile flavor compounds of the fermented wheat bran were subsequently analyzed using SPME/GCMS. The combination of L. plantarum HNGD-CQ and S. cerevisiae HNGD-JZ was identified as the optimal fermentation strain pair. After fermentation, the IC₅₀ for DPPH· of wheat bran was 46.35 μL/mL, the IC₅₀ for ABTS· was 5.59 μL/mL, and the reducing power reached 3.94 mmol/g. The fermentation process was systematically optimized through single-factor experiments followed by Box-Behnken response surface methodology. The optimal fermentation conditions were determined as a total inoculation amount of 10.6%, an inoculation ratio of S. cerevisiae to L. plantarum of 2.3:1, a fermentation temperature of 30℃, and a fermentation duration of 3 days. Under these conditions, the IC₅₀ for DPPH· value of the fermented wheat bran decreased to 38.21 μL/mL, representing a 17.5% reduction compared with pre-optimization levels and indicating a significant increase in antioxidant activity (P<0.05). Volatile organic compounds in the samples were analyzed using SPME/GC-MS. The results demonstrated that co-fermentation significantly increased the concentrations of desirable aromatic compounds, such as alcohols (116.39 μg/g) and esters (19.08 μg/g), while reducing the levels of off-flavors components including aldehydes and hydrocarbons by 63.75% and 32.14%, respectively. This study demonstrates that co-fermentation of wheat bran with L. plantarum HNGD-CQ and S. cerevisiae HNGD-JZ not only significantly enhances its antioxidant potential but also improves its volatile flavor profile, providing valuable microbial resources and process conditions for the high-value utilization of wheat bran in functional food development.