Wild artisanal cultures, such as a symbiotic culture of bacteria and yeasts (SCOBY) and water kefir grains (WKG), represent a complex microorganism consortia that is composed of yeasts and lactic and acetic acid bacteria, with large strains of diversity and abundance. The fermented products (FPs) obtained by the microbiome’s contribution can be included in functional products due to their meta-biotics (pre-, pro-, post-, and paraprobiotics) as a result of complex and synergistic associations as well as due to the metabolic functionality. In this study, consortia of both SCOBY and WKG were involved in the co-fermentation of a newly formulated substrate that was further analysed, aiming at increasing the postbiotic composition of the FPs. Plackett–Burman (PBD) and Response Surface Methodology (RSM) techniques were employed for the experimental designs to select and optimise several parameters that have an influence on the lyophilised starter cultures of SCOBY and WKG activity as a multiple inoculum. Tea concentration (1–3%), sugar concentration (5–10%), raisins concentration (3–6%), SCOBY lyophilised culture concentration (0.2–0.5%), WKG lyophilised culture concentration (0.2–0.5%), and fermentation time (5–7 days) were considered the independent variables for mathematical analysis and fermentation conditions’ optimisation. Antimicrobial activity againstBacillus subtilisMIUG B1,Staphylococcus aureusATCC 25923,Escherichia coliATCC 25922, andAspergillus nigerMIUG M5, antioxidant capacity (DPPH), pH and the total acidity (TA) were evaluated as responses. The rich postbiotic bioactive composition of the FP obtained in optimised biotechnological conditions highlighted the usefulness of the artisanal co-cultures, through their symbiotic metabolic interactions for the improvement of bioactive potential.