This work studied the antibacterial performance and mechanical properties of natural rubber (NR) compound reinforced with commercial silica at various silica loadings form 0, 20, 40 and 60 parts per hundred rubber (phr). 2-Hydroxypropyl-3-Piperazinyl-Quinoline carboxylic acid Methacrylate (HPQM) based Neusilin at loadings of 0, 3 and 5 phr were used as anti-bacterial agent against Escherichaia coli (E.coli) ATCC 25923 and Staphylococcus aureus (S.aureus) ATCC 25922. The antibacterial performance was reported as a clear zone radius by diffusion test and a percentage reduction of bacteria by Plate-Count-Agar (PCA) method. The results suggested that the increasing silica loading in the NR vulcanizates improved the tensile modulus and hardness, but decreased elongation which had optimal tensile strength at 20 phr of silica. Additionally, the HPQM based Neusilin did not affect the mechanical properties of the rubber vulcanizates. The antibacterial results showed that the inhibition zone radius and the percentage reduction increased with increasing HPQM based Neusilin, but decreased with silica filler content. The antibacterial efficacy was inversely related to the reinforcement level of the NR vulcanizates by the silica. The percentage reduction of bacteria of NR compound filled with 5 phr of HPQM based Neusilin achieved 99.9%.