The lack of a transparent, flexible, and reliable encapsulation layer for organic-based devices makes it difficult to commercialize wearable, transparent, flexible displays. The reliability of organic-based devices sensitive to water vapor and oxygen must be guaranteed through an additional encapsulation layer for the luminance efficiency and lifetime. Especially, one of the major difficulties in current and future OLED applications has been the absence of thin-film encapsulation with superior barrier performance, mechanical flexibility, and water-resistant properties. In this work, we fabricated highly water-resistant, impermeable, and flexible inorganic/organic multilayers with optimized Al2O3 and functional organic layers. The key properties of the fabricated multilayers were compared according to the thickness and functionality of the inorganic and organic layers. Improvement of the barrier performance is mainly attributed to the optimized thickness of the Al2O3 films, and is additionally due to the increased lag time and effective surface planarization effects caused by the use of micrometer-thick organic layers. As a result, the 3-dyad multilayer structure composed of 60 nm-thick Al2O3 layers deposited at 70 °C and 2-μm-thick silane-based inorganic/organic hybrid polymer (silamer) layers with layered silica exhibited the lowest WVTR value of 1.11 × 10-6 g/m2/day in storage conditions of 30 °C/90% relative humidity. In addition, the multibarrier exhibited good mechanical stability through the use of alternating stacks of brittle inorganic and soft organic layers, without showing a large increase in the WVTR after bending tests. In addition, silamer layers improved the environmental stability of the Al2O3 ALD film. The silamer layer coated on the Al2O3 film effectively worked as a protective layer against harsh environments. The effective contact at the interface of Al2O3/silamer makes the barrier structure more impermeable and corrosion-resistant. In this study, we not only demonstrated an optimized multilayer based on functional organic layers but also provided a methodology for designing a wearable encapsulation applicable to wearable organic electronics.