This research investigates how different fermentation techniques using non-Saccharomyces yeast (Candida ethanolica Ce, Hanseniaspora guilliermondii Hg, Hanseniaspora thailandica Ht) and Saccharomyces cerevisiae (Sc) affect the synthesis of hesperidin, nobiletin, and other flavonoid and aromatic substances, which play a vital role in improving the overall quality of fruit wines due to their various biological properties. The combination of Sc:(Ce.Ht)-1:100 (Ce 0.5 × 107 CFU/mL, Ht 0.5 × 107 CFU/mL, Sc 1 × 105 CFU/mL) yielded the highest hesperidin content at 4.12 ± 0.08 mg/L, followed by the Sc:(Ce.Hg)-1:1 (Ce 0.5 × 107 CFU/mL, Hg 0.5 × 107 CFU/mL, Sc 1 × 107 CFU/mL) combination at 4.08 ± 0.06 mg/L. The highest nobiletin content was achieved by the (Hg.Ht)-10-Sc (Hg 0.5 × 107 CFU/mL, Ht 0.5 × 107 CFU/mL, Sc 1 × 107 CFU/mL) combination, reaching 1.04 ± 0.05 mg/L, which was significantly higher than other multi-strain combinations. Additionally, the hesperidin content produced by the (Hg.Ht)-10-Sc combination was relatively high at 4.04 ± 0.02 mg/L, demonstrating a richness and complexity of aroma superior to that of fermentation with commercial yeast strains alone. The findings suggest that the (Hg.Ht)-10-Sc combination is the most effective multi-strain combination for increasing the levels of nobiletin and hesperidin in citrus wine, thereby enhancing the overall quality of the wine. These experimental results offer a promising approach for enhancing the quality of citrus wines and other fruit wines.