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Osmotic stress in the yeast limits productivity in industrial beer production under very high gravity brewing. This study focused on assessing the protective impacts of eleven plant-derived antioxidant dipeptides (PADs) on the osmotic stress tolerance of lager yeast. The results showed that PADs provided yeast with stress tolerance under osmotic stress. PADs supplementation enhanced cell membrane integrity and reduced oxidative damage. PADs upregulated the expression of SOD2, PEX11 and CTT1 genes under osmotic stress. Moreover, the volatile compounds contents and antioxidant activities of beers were improved by PADs, suggesting favorable quality characteristics. Especially, Phe-Cys and Leu-His could increase the DPPH radical scavenging activity of beer by 41.92% and 18.78% respectively, compared with control. Therefore, PADs are industrially scalable enhancers to improve the ability of yeast to resist osmotic stress and beer quality during very high gravity brewing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)