The extract of Piper betle leaf possesses antibacterial and antioxidant properties. Piper belle plant is one of the most useful herbal remedies for skin disorder because it can inhibit the growth of microorganism. The objective of this study is to formulate and characterize the Sirih (Piper belle) oil nanocream and to test the effectiveness of the nanocream containing Sirih (Piper betle) oil on antimicrobial activities. Essential oil of the Piper belle was extracted by using steam distillation method. Formulation of nanoemulsions used was 60% of surfactants, 30% of distilled water and 10% of oil. Surfactants used were a mixture of Tween 80 and glycerol. For the nanoemulsion containing the Piper belle oil, the ratio of 1:4(R1) and 1:1(R2) is produced in the oil phase. It was the ratio of Piper betle oil to soybean oil. The diluted nanoemulsion was further used in production of nanocream. The diluted nanoemulsion at ratio of 0.03 was added with saboflow at different ratios of 7:3, 8:2 and 9:1 The formulation of 9:1 ratio of diluted nanoemulsion to saboflow was incorporated with the R1 and R2 nanoemulsions. The characacterization on the physical appearance, tyndall effect and droplet size was measured for nanoemulsions and nanocream. Staphylococcus aureus was used to test the effectiveness of the nanocream containing Piper belle oil on antimicrobial activities. The nanocream containing the Piper belle oil show the inhibition zone at average of 0.567cm for R1 and 0.867cm for R2. Thus, the results indicate that Piper betle nanocream can be used to treat skin infection.