The hydrocarbon-based economy is moving at a large pace to a decarbonized sustainable bioeconomy based on biorefining all types of secondary carbohydrate-based raw materials. In this work, 50 g L−1 in COD of a mixture of food waste, brine and wastewater derived from a biodiesel production facility were used to produce organic acids, important building-blocks for a biobased industry. High salinity (12–18 g L−1), different reactors configuration operated in batch mode, and different initial pH were tested. In experiment I, a batch stirred reactor (BSR) at atmospheric pressure and a granular sludge bed column (GSBC) were tested with an initial pH of 5. In the end of the experiment, the acidification yield (ηa) was similar in both reactors (22–24%, w/w); nevertheless, lactic acid was in lower concentrations in BSR (6.3 g L−1 in COD), when compared to GSBC (8.0 g L−1 in COD), and valeric was the dominant acid, reaching 17.3% (w/w) in the BSR. In experiment II, the BSR and a pressurized batch stirred reactor (PBSR, operated at 6 bar) were tested with initial pH 7. The ηa and the VFA concentration were higher in the BSR (46%, 22.8 g L−1 in COD) than in the PBSR (41%, 20.3 g/L in COD), and longer chain acids were more predominant in BSR (24.4% butyric, 6.7% valeric, and 6.2% caproic acids) than in PBSR (23.2%, 6.2%, and 4.2%, respectively). The results show that initial pH of 7 allows achieving higher ηa, and the BSR presents the most suitable reactor among tested configurations to produce VFA from wastes/wastewaters with high salinity.