In the European Union, Israel and India, testing cosmetic products or their ingredients on animals is prohibited. In this context, in vitro cell models play a pivotal role in the evaluation of both safety and beneficial effects of cosmetics. Oily formulations, widely used in cosmetics, are complex to study on cell models due to their lipophilic nature that doesn’t match with hydrophilic culture medium. Organic solvents are then required to solubilize oily formulations, but they can interfere with the cellular response. To avoid the use of organic solvents, we developed a method based on cells to evaluate potential beneficial effects of oily formulations. Our method, suitable for high throughput screening, consists in: (1) incubating cells with oily formulations for a short time followed by a recovery period in culture medium and (2) studying cell parameters using robust techniques such as cytofluorometry and fluorescence resonance energy transfer (FRET). Depending on the studied cell parameter, various beneficial effects can be revealed like antioxidant, anti-inflammatory and skin regeneration. The field of cell parameters is open and can be extended to new perspectives in the development of oily formulations.