Biocontrol strategies for the limitation of undesired microbial developments in foods and beverages represent a keystone toward the goal of more sustainable food systems. Brettanomyces bruxellensis is a wine spoilage microorganism that produces several compounds that are detrimental for the organoleptic quality of the wine, including some classes of volatile phenols. To control the proliferation of this yeast, sulfur dioxide is commonly employed, but the efficiency of this compound depends on the B. bruxellensis strain; and it is subject to wine composition and may induce the entrance in a viable, but nonculturable state of yeasts. Moreover, it can also elicit allergic reactions in humans. In recent years, biological alternatives to sulfur dioxide such as the use of yeasts and lactic acid bacteria starter cultures as biocontrol agents are being investigated. The controlled inoculation of starter cultures allows secure, fast and complete alcoholic and malolactic fermentations, limiting the residual nutrients that B. bruxellensis utilizes to survive and grow in wine. The current study is focused on the assessment of the effect of autochthonous yeasts and bacterial strains from the Apulia Region on the development of B. bruxellensis in wine, in terms of both growth and volatile phenols' production. The investigation evidences the positive role of indigenous mixed cultures in the control of this spoilage yeast, either co-inoculating different strains of Saccharomyces cerevisiae, S. cerevisiae/non-Saccharomyces or co-inoculating S. cerevisiae/Oenococcus oeni. Our findings expand the existing knowledge of the application of protechnological microbial diversity and of non-Saccharomyces as a biocontrol agent in oenology. We report a further demonstration of the interest in selecting indigenous strains as a strategic tool for winemakers interested in the improvement of regional wines.