There is a growing emphasis on the development of coatings that impart diverse functionality to medical devices. In particular, coatings for medical devices, which exhibit enhanced mechanical properties and antibacterial effects, are one of the most impactful technologies because they enable long-term use of medical devices and protect patients from infection. Polysilsesquioxane (PSQ), an organic/inorganic hybrid material is regarded as a promising candidate for materials of various functional coatings owing to its functionality and excellent mechanical properties. In this study, we fabricated durable PSQ hybrid coatings with controlled superwettability for medical devices. First, well-defined PSQ matrices were synthesized via sol.gel reaction. Two types of PSQ solutions used for coatings were prepared by selectively using three precursors. Subsequently, superhydrophilic and superhydrophobic coatings with an antibacterial property were prepared via a facile one-step dipping method without any thermal treatment using two prepared PSQ coating solutions. We attempted to develop PSQ mono-coatings that exhibit both antibacterial activity and durability using a controlled experimental design. Therefore, this study introduces the promising applicability of PSQ in the field of medical coatings.