Nowadays, a global trend in the chemical industry is the search for and implementation of methods that are environmentally benign and consistent with the principles of green chemistry. In response to this concept, environmentally friendly deep eutectic solvents (DESs) enable chemical processes to be conducted under mild, non-toxic conditions, and thus align with the philosophy of green chemistry. This study aimed to evaluate the applicability of eutectic mixtures based on choline chloride or tetramethylammonium chloride as hydrogen bond acceptors (HBA) in oxidation processes. The oxidation of ethylbenzene with oxygen was selected as a model reaction, leading to a mixture of acetophenone, 1-phenylethanol, ethylbenzene hydroperoxide, benzaldehyde, and benzoic acid. The results demonstrate that the use of a DES composed of choline chloride and triethylene glycol, in combination with cobalt(II) chloride or cobalt(II) acetylacetonate, enables the achievement of relatively high ethylbenzene conversion (20.3-26.3%) along with high selectivity toward the main product, acetophenone (88.7-91.2%). Furthermore, the study confirmed that both the substrate loading and the amount of eutectic mixture have a significant impact on conversion and on the composition of ethylbenzene oxidation products. The obtained results indicate that the DES system based on choline chloride and triethylene glycol can be recovered and reused up to six times without a significant loss of catalytic activity.