Objective: Formulation, antibacterial activity, and stability tests of niosomal gels containing betel leaf (Piper betle L.) essential oil as an anti-acnetreatment were carried out. Niosome vesicular carriers provide drug delivery through the topical and transdermal routes. The aim of creating theniosome preparation was to increase the transfollicular penetration and improve the stability of the gel.Materials and Methods: Betel leaf essential oil extraction was performed using the steam distillation method, and essential oil compoundidentification was completed using gas chromatography–mass spectrometry. The niosome formulations were generated with two cholesterol–surfactant amount ratios, specifically, 1:1 (F1) and 1:2 (F2; w/w). The niosomes were evaluated, including the entrapment efficiency test, usingultraviolet-visible spectrophotometry; particle size analysis was performed using a particle size analyzer; and the vesicle morphology test wasconducted using transmission electron microscopy. The niosomes were made into a gel using 0.5% carbopol 940 as the gelling agent. The niosomegels were evaluated for their organoleptic properties, pH, viscosity, antibacterial activity against Propionibacterium acnes, and stability for 12 weeksat three different storage temperatures, namely, low temperature (4±2°C), room temperature (28±2°C), and high temperature (40±2°C).Results: The test results showed that the F2 niosome gel was more stable than the F1 gel was, while the antibacterial activities of the F1 and F2niosome gels did not differ significantly.Conclusion: The niosomal gel preparations’ inhibition of the growth of P. acnes bacteria was decreased compared with that of the essential oils.