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Mead exhibits bioactive potential due to the composition of honey and the changes brought about by fermentation; however, the presence of ethanol may mitigate the expression of this potential, underscoring the need for de-alcoholization strategies that preserve its functional characteristics. The objective of this study was to optimize the de-alcoholization of mead by vacuum distillation and to evaluate its effects on the phenolic profile and antioxidant activity. Wild honey wort (20 °Brix) was fermented with Saccharomyces cerevisiae (0.5 g/L) until the sugar was completely consumed. The resulting mead (9.1% alcohol and 215.1 mg/L of phenolics) was subjected to vacuum distillation using a Rotational Central Composite Design (DCCR) 2², with time (9–16 min) and temperature (52.8–61.2 °C) as independent factors, including axial points and three replicates at the central point. Alcohol content (ebuliometry) and total phenolics (HPLC-DAD) were evaluated as responses, and the data were analyzed using Response Surface Methodology (RSM). Control meads (C), along with those with higher (+D) and lower (-D) de-alcoholization intensity, were evaluated for phenolic profile (HPLC-DAD), antioxidant activity (DPPH, FRAP, ABTS, and ORAC), and color (CIELAB). The results were analyzed using ANOVA, Tukey’s test, and a heatmap. The highest de-alcoholization efficiency was obtained at 60 °C for 15 min, reducing the alcohol content to 0.9% (+D), while the lowest efficiency occurred at 52.8 °C for 12.5 min, leaving 5.5% alcohol (-D), with total phenolic contents of 217.1 and 206.6 mg/L, respectively. Temperature was the factor with the greatest influence on ethanol reduction, with a positive linear effect of both temperature and time. For total phenolics, only temperature was significant, with higher levels under intermediate conditions, possibly related to the release of bound phenolic compounds or the transformation of more complex structures. The heatmap revealed significant changes in the phenolic profile after dealcoholization: compounds present in the control, such as hydroxybenzoic acids, hydroxycinnamic acids, and quercetin, were reduced, while +D exhibited higher levels of gallic acid, catechin derivatives, phenolic acids, and 2,4-dihydroxybenzoic acid, suggesting the transformation or release of different phenolic forms during heat treatment. Although DPPH and FRAP values did not differ among the samples, -D exhibited higher ABTS activity, and +D exhibited higher ORAC activity, indicating that changes in the composition and structure of phenolics can alter their reactivity with respect to different antioxidant mechanisms. In the color assessment, dealcoholization reduced L* and the hue angle (h°) and increased a*, b*, and C* (p<0.05), indicating slight darkening and greater chromatic intensity. Therefore, vacuum distillation reduced the alcohol content and modulated the phenolic and antioxidant profiles of the mead, demonstrating potential for producing a non-alcoholic beverage with bioactive properties.
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