Background Water kefir (WK) is a traditional plant-based fermented beverage. This study used genome-scale modeling (GSM) to design minimal synthetic microbial communities (SynComs) for novel WK fermentations. These SynComs were then validated through multi-omics analyses following fermentation with two sustainable substrates from Ireland. The aim was to assess the performance of GSM-designed SynComs in terms of fermentation efficiency (e.g., acidification and microbial growth), and to evaluate the safety and health-promoting potential of the resulting beverages. Methods Six SynComs were used for the fermentation of two sustainable substrates. The pH and viable colony-forming units were monitored throughout the fermentation. The ethanol and residual sugar contents were quantified using HPLC. Shotgun metagenome sequencing was performed to confirm the community composition after fermentation. Safety assessments, including mycotoxin screening and cytotoxicity evaluations using a gut epithelial cell model, were also performed. Gut microbiota modulatory effects of the fermented foods were evaluated using an ex vivo model of the distal colon. A comprehensive metabolomic analysis was performed to quantify non-volatiles, volatiles, and organic acids. Results All SynComs successfully fermented the novel WK, lowering pH to ~3.5. Ethanol content remained within the non-alcoholic range (<0.3% ABV), and the sucrose content was ~0.5%, resulting in non-alcoholic, low-sugar beverages. Shotgun metagenomics and microbial culturing confirmed SynCom composition. No mycotoxins and cytotoxicity detected. Metabolomic analysis revealed the presence of favorable health-promoting compounds and volatiles, resulting in promising novel WKs.  Conclusion This study demonstrates the successful application of SynComs for the fermentation of novel, healthy, and sustainable WK.