High-pressure processing (HPP) is considered as gentle preservation technique for especially heat-sensitive food ingredients. So far, the focus has been on the fact that it is called a nonthermal process and high pressure can affect bioavailability, but it is questionable whether the high pressure affects the ingredients themselves. By using an o/w-microemulsion (ME) as a model system, it was possible to investigate the influence of pressure, especially on lipophilic compounds (e.g., carotenoids and vitamin E), without the complexity of a food matrix. The ME consisted of Capryol® TM 90, Tween® 80 or 20, Transcutol® HP and distilled water. Lipophilic and hydrophilic compounds were introduced to the oil phase and to the aqueous phase, respectively. Storage experiments confirmed the applicability for β-carotene and α-tocopherol. HPP of MEs, performed for 10 min at room temperature (RT) and up to 600 MPa, resulted in pressure stability of β-carotene (exceptional at 400 MPa; −11%) and α-tocopherol. Multicomponent ME showed that both had a positive effect on the stability of chlorophyll a/b during HPP. An ME environment was used to facilitate co-oxidation of β-carotene via lipoxygenase (LOX) from an Edamame-based crude enzyme extract and lyophilized LOX-1 from soybeans during storage (RT and 4°C, dark conditions) and HPP treatment. A loss of β-carotene occurred after addition of linoleic acid, whereas effects of added α-tocopherol could be related to β-carotene protection. Overall, the introduced ME for studying HPP effects on lipophilic food ingredients showed promising results as versatile model system for future investigations regarding interactions of phytochemicals.