The aim of this study was to evaluate the physico-mechanical, anti-bacterial, and anti-demineralization properties of orthodontic resin composite containing photoactivated zinc oxide nanoparticles (ZnONPs) on Streptococcus mutans biofilm around ceramic and metal brackets. Following the minimum inhibitory concentration (MIC) determination for ZnONPs, shear bond strength (SBS) was tested for composites containing different concentrations of ZnONPs. The chosen concentration was used to evaluate the microleakage, anti-bacterial, and anti-demineralization properties. Adding 50μg/mL of ZnONPs to the orthodontic composite did not negatively affect its physico-mechanical properties. ZnONPs (50μg/mL)-mediated aPDT and 0.2% chlorhexidine significantly (P=0.000) reduced S.mutans biofilms compared to the phosphate-buffered saline (PBS) groups (metal/PBS=7.47±0.7×106, and ceramic/PBS=7.47±0.7×106), with the lowest colony count observed in these groups (metal/chlorhexidine=1.06±0.4×105, ceramic/chlorhexidine=1±0.2×105, metal/ZnONPs-mediated aPDT=1.33±0.3×105, and ceramic/ZnONPs-mediated aPDT=1.2±0.3×105). Sodium fluoride varnish and ZnONPs-mediated aPDT showed the highest efficacy in anti-demineralization and significantly improving the enamel surface microhardness compared to the artificial saliva, especially in ceramic bracket groups (524.17±42.78N and 441.00±29.48N, 394.17±46.83N, P=0.000, and P=0.003, respectively). ZnONPs (50μg/mL)-mediated aPDT effectively inhibited S.mutans biofilm and promoted anti-demineralization without adverse effects on the physico-mechanical properties of the composite resin. These results suggest the potential of this method in preventing white spot lesions during orthodontic treatment.