Parylene C (PC) has attracted tremendous attention throughout the past few years due to its extraordinary properties such as high mechanical strength and biocompatibility. When used as a flexible substrate and combined with high-κ dielectrics such as aluminum oxide (Al2O3), the Al2O3/PC stack becomes very compelling for various applications in fields such as biomedical microsystems and microelectronics. For the latter, the atomic layer deposition of oxides is particularly needed as it allows the deposition of high-quality and nanometer-scale oxide thicknesses. In this work, atomic layer deposition (ALD) and electron beam physical vapor deposition (EBPVD) of Al2O3 on a 15 μm-thick PC layer are realized and their effects on the Al2O3/PC resulting stack are investigated via X-ray photoelectron spectroscopy combined with atomic force microscopy. An ALD-based Al2O3/PC stack is found to result in a nanopillar-shaped surface, while an EBPVD-based Al2O3/PC stack yields an expected smooth surface. In both cases, the Al2O3/PC stack can be easily peeled off from the reusable SiO2 substrate, resulting in a flexible Al2O3/PC film. These fabrication processes are economic, high yielding, and suitable for mass production. Although ALD is particularly appreciated in the semiconducting industry, EBPVD is here found to be better for the realization of the Al2O3/PC flexible substrate for micro- and nanoelectronics.