The modification of polymer with nanoparticles has been proved to have good results, but the key of this method is that nanoparticles can maintain uniform dispersion in the polymer. Herein, silica (SiO2 ) and zinc oxide (ZnO) hybrid nanofillers were prepared by self-made dispersion equipment to modify natural rubber latex (NRL). The results show that the uniformly dispersed nano-SiO2 fillers increase the number of entanglements in the molecular chain of NRL, thereby improving the tensile properties. The tensile strength and elongation at break of LZ1S4.2 were increased to 32.61 MPa and 957%, respectively. The increase of the number of entanglements also makes the structure of NRL more compact, and improves the barrier performance and aging resistance. The uniformly dispersed nano-ZnO fillers endow the NRL with excellent antibacterial properties, and the antibacterial rate (For Escherichia coli and Staphylococcus aureus ) is greater than 99.9%. In addition, NRL condoms and gloves incorporating hybrid nanofillers have been proved to have good biocompatibility, and this NRL nanocomposite is expected to be applied to other NRL products.