Abstract: Compromised food safety has posed a major threat to public health worldwide. A variety of foodborne pathogens (e.g., Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes) can frequently contaminate the raw materials during food processing, particularly after compromised supply chains or inadequate hygiene practices. These microbes can survive at processing stages and, upon consumption, trigger severe gastrointestinal infections, systemic illnesses, or even fatal outcomes, particularly in vulnerable populations like children and the elderly. While the conventional sterilization is often limited to nutrient degradation and undesirable alterations in food quality. In contrast, the emerging non-thermal sterilization, such as the photodynamic treatment (PDT) or sonodynamic treatment (SDT), can effectively inactivate the foodborne pathogenic bacteria, while preserving the nutritional and sensory qualities of the food products. The PDT can operate via a light-activated mechanism: photosensitizers, upon absorption of the specific wavelengths of light, can undergo a photochemical transition to generate the reactive oxygen species (ROS), primarily singlet oxygen and hydroxyl radicals. While the SDT can use the ultrasonic waves for cavitation and mechanical damage to pathogens. However, the inactivation efficacy of the PDT and SDT can vary in the food matrices due to the complexity and heterogeneity of the food matrices. The underlying mechanisms also remain unclear. In the present study, the blue pigment and guar gum were employed to construct the food matrices with variable optical transmittance and viscosity. A systematic investigation was also made on the bactericidal efficiency of the curcumin-mediated PDT and SDT against Staphylococcus aureus under different food matrix conditions. Firstly, the model systems were prepared with the different transmittance (blue pigment gradient: 0.006 25-0.050 00%) and viscosity (guar gum gradient: 0.2%-0.8%). Absorbance was then measured by spectrophotometry. The viscosity was determined by rotational viscometry. Results showed that the increasing concentration of the blue pigment (0.006 25 %-0.050 00 %) shared no significant variation in the viscosity. Conversely, the increasing concentration of the guar gum (0.2%-0.8%) led to the nonlinear increase in the viscosity. While the transmittance remained unchanged. Subsequent treatments involved the curcumin at a concentration of 50 μmol/L as the sensitizing agent, activated by a 425 nm LED light source at an intensity of 5.3 mW/cm², combined with ultrasound at 45 kHz and 0.40 W/cm² for 30 min. The results show that the increasing concentrations of the blue pigment (0.006 25%-0.050 00%) significantly impaired the PDT efficacy, due to the reduced light penetration, whereas the SDT was largely unaffected under the same optical conditions. In contrast, the higher guar gum concentrations (0.2%-0.8%) significantly hindered the SDT efficiency by impeding ultrasonic transmission, while the PDT remained comparatively stable in the bactericidal performance. In addition, the light transmittance and PDT shared a strong correlation after the Pearson correlation of the light transmittance/viscosity and photo-/SDT. While the viscosity showed a strong correlation with the SDT. In summary, the optical transmittance was identified as the main influencing factor on the photodynamic performance. While the substrate viscosity is the key influencing factor on the sonodynamic performance. These findings can greatly contribute to the valuable reference data for the photo- and sonodynamic technologies in diverse food matrices.