Combined therapies are usually used to treat acne vulgaris since this approach can tackle various foci simultaneously. Using a combination of spectroscopic, computational, and microbiological techniques and methods, herein we report on the use of β-lactoglobulin as a double payload carrier of hypericin (an antimicrobial photodynamic agent) and all-trans retinoic acid (an anti-inflammatory drug) for S. aureus in vitro photodynamic inactivation. The addition of all-trans retinoic acid to hypericinβ-lactoglobulin complex renders a photochemically safe vehicle due to the photophysical quenching of hypericin, which recovers its photodynamic activity when in contact with bacteria. The ability of hypericin to photoinactivate S. aureus was not affected by retinoic acid. β-Lactoglobulin is a novel biocompatible and photochemically safe nanovehicle with strong potential for the treatment of acne.