<p>Twelve selected natural flavonoids (<b>F1</b>–<b>F12</b>) and their brominated derivatives (<b>F1a</b>–<b>F12a</b>) were investigated for their antidiabetic effects on <i>α</i>-glucosidase and <i>α</i>-amylase, as well as anti-glycation activity. The semisynthetic brominated flavonoids (<b>F1a</b>–<b>F12a</b>) were synthesized using brominating agents. Among the semisynthesized compounds, two semisynthetic compounds including 6,8-dibromoluteolin (<b>F3a</b>) and 6,8-dibromoalpinetin (<b>F10a</b>) were reported as new compounds. 8-Bromobaicalein (<b>F4a</b>, IC₅₀ = 0.52 ± 0.05 µM) and 6,8-dibromoluteolin (<b>F3a</b>, IC₅₀ = 0.99 ± 0.12 µM) were found as mixed-type potent agents on <i>α</i>-glucosidase and <i>α</i>-amylase inhibitory activities, respectively. In addition, 6,8-dibromochrysin (<b>F1a</b>, IC₅₀ = 50.90 ± 0.98 µM) was found to be the most potent compound for inhibiting Bovine Serum Albumin - glycation (BSA-glycation) mediated methylglyoxal. The results of this study indicated that the introduction of bromine into flavonoids could benefit antidiabetic and anti-glycation due to the influence of the electronic effect and hydrophobic properties of bromine atoms.</p>