Water kefir (WK) is a traditional fermented beverage, well-known for its potential health benefits. This study focused on the isolation of cultivable microbes from traditional water kefir grains and reassembling them into minimal, defined synthetic microbial communities (SynComs). These SynComs were then used for the fermentation of novel WK beverage using two food waste-based substrates from Ireland. We also used multi-omics analyses to validate the performance of the SynComs in terms of fermentation efficiency and to evaluate the safety and health-promoting potential of the resulting beverages. Six SynComs were developed using the genome-scale metabolic modelling (GSMM) approach and used for the novel WK fermentation. Shotgun metagenome sequencing was performed to identify the community composition after fermentation. Safety assessments, including mycotoxin screening and cytotoxicity evaluations, were also performed. Gut microbiome modulatory effects were evaluated using an ex vivo model of the distal colon. A comprehensive metabolomic analysis was performed to quantify non-volatile and volatile compounds. 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 below 5g/l, resulting in non-alcoholic, low-sugar beverages. Shotgun metagenomics confirmed SynCom composition. No mycotoxins and cytotoxicity were detected in any of the resulting WK. Metabolomic analysis revealed the presence of favourable health-promoting compounds and volatiles, resulting in promising novel beverages. This study demonstrates the successful application of GSMM-guided SynComs to transform food waste-based substrates into novel, healthy, and sustainable fermented foods.