CuO/MgAl2O4 and CuO/MgFe2O4 catalysts were successfully synthesized with the use of spinel supports by a very simple and low-cost mechanochemical method. High-speed ball-milling was used to synthesize these catalyst supports for the first time. Materials were subsequently characterized by using XRD, FESEM, TEM, EDS-Dot mapping, XPS, BET-BJH, and Magnetic Susceptibility to investigate the physical-chemical characteristics of the catalysts. Acidity evaluation results indicated that the catalyst with the Mg-Al spinel support had more acid sites. XRD results showed a successful synthesis of the catalysts with large crystal sizes. Both catalysts were used in isoeugenol oxidation and vanillyl alcohol to vanillin reactions, with the CuO/MgAl2O4 showing optimum results. This catalyst provided 67% conversion (74% selectivity) after 2 h and this value improved to 81% (selectivity 100%) with the second reaction after 8 h. The CuO/MgFe2O4 catalyst in the first reaction after five hours revealed 53% conversion (47% selectivity) and after eight hours with the second reaction, the conversion value improved to 64% (100% selectivity). In terms of reusability, CuO/MgAl2O4 showed better results than the CuO/MgFe2O4 catalyst, for both reactions.