Background/Objectives: Curcumin is a food-grade (E100) photosensitiser with promising antimicrobial properties, but its applicability is limited due to low water-solubility. Complexation of curcumin with hydroxypropyl-γ-cyclodextrin (HP-γ-CD) overcomes this constraint and may facilitate using a single photosensitiser for Photodynamic Inactivation (PDI) of pathogens along the food-production chain and within a One Health framework. Methods: In this study, a novel method to complex HP-γ-CD and curcumin (abbreviated as CD-Cur) was developed and the compound was tested against Escherichia coli, Salmonella enterica, and Candidozyma auris, in liquid culture and in situ on abiotic surfaces, food matrices, and a porcine skin model. Results: Planktonic experiments demonstrated concentration-dependent PDI efficacy with photokilling exceeding the 3 log₁₀ threshold for all tested organisms at CD-Cur concentrations between 10 and 50 µM, illuminated with 435 nm (50 J/cm²) LED light, while dark and light toxicity remained below microbiologically relevant levels. CD-Cur induced high reductions of viable E. coli on food-contact plastic foil (3.35 log₁₀, 100 µM, white light, 100 J/cm²) and on abiotic surfaces (5.17–5.50 log₁₀, 30 µM, 435 nm, 25 J/cm²) with visible photobleaching of the photosensitiser after illumination. On salmon and pistachios, matrix-dependent effects were observed, but PDI still achieved practically relevant reductions (2.25–3.52 log₁₀, 30 µM, 435 nm, 200 J/cm²) of S. enterica without visible colour alteration of the food. In a porcine skin model, CD-Cur in a 1% hydroxyethyl cellulose hydrogel reduced C. auris contamination notably. The addition of 2 mM EDTA further enhanced antifungal effects, indicating that CD-Cur can also be applied in a medical context as topical application on porcine skin (2.41 log₁₀, 500 µM, 435 nm, 75 J/cm²). Conclusions: Together, these results show that a single, photodynamic system based on food-grade CD-Cur can provide broad antimicrobial efficacy across diverse matrices and pathogens in a One Health context.