In this work, we address the issue of controlled modification of the surface topography of polydimethylsiloxane (PDMS) when subjected to oxygen-based plasma treatments, and we investigate the resulting enhanced surface area as a means of controlling the surface wetting properties. We fabricate wavy structures of controllable nanoscale amplitude and periodicity in the range 50-300 nm, spontaneously formed on PDMS surfaces, by means of appropriate plasma processing conditions and radiation pretreatment. Such structures are desirable for applications in sensor microdevices, the development of biocompatible materials, and micro- and nanosystems in general. Ordered structures fabricated on polydimethylsiloxane of relatively high amplitude and small periodicity are chosen as appropriate surfaces for the enhancement of the surface wetting properties, which can be tuned from highly hydrophilic to hydrophobic when combined with a hydrophobic coating applied on the rich surface nanotexture. This fact underlines the potential application of the proposed technique in the field of microfluidics, where polydimethylsiloxane is gaining popularity as structural material for microfluidic devices.