The bio-composite films based on Hydroxypropyl methylcellulose (HPMC) reinforced with silver nanoparticles (AgNPs) and Titanium oxide nanoparticles (TiO2-NPs) were developed. Some physical and mechanical properties: Tensile strength (TS), elongation (E), Young’s elastic modulus (EM), water vapor permeability (WVP) and transparency were determined. Antibacterial properties of these films were also studied. The tensile strength values of HPMC film reinforced with Ag NPs and TiO2-NPs and HPMC without nanoparticles were 39.24, 143.87 and 157.92 MPa, respectively. Elongation of the HMPC film was less than the HPMC film reinforced with AgNPs and TiO2-NPs, the results were 2, 35 and 42%, respectively. Additionally, Young’s elastic modulus of HMPC film was determined to be 19.62 MPa and the HPMC film reinforced with AgNPs and TiO2-NPs were 4.11 and 3.76 MPa, respectively. The values of WVP of HMPC film was higher than the HMPC film reinforced with AgNPs and TiO2-NPs, where they were 0.5076 × 10−3, 0.4596 × 10−3 and 0.4504 × 10−3 (g/msPa), respectively. Nano-composite films demonstrated strong antibacterial activity against tested pathogen bacteria in the contact surface zone. The antibacterial activites of AgNPs (~ 10 nm) at 80 ppm were more active than 20 and 40 ppm against foodborne pathogen i.e. Bacillus cereus and Escherichia coli, the inhibition zone diameters were 9 and 10 mm, respectively. As well, TiO2-NPs (~ 50 nm) at 80 ppm were more active than 20 and 40 ppm against B. cereus and Salmonella Typhimurium, the inhibition zone diameters were11 and 10 mm, respectively.