The use of biodegradable and biocompatible materials for electronic applications is a research topic of great interest, offering the possibility to develop bio-electronic devices and reduce e-wastes. In this work, poly(lactic acid) (PLA) films were prepared to be employed as substrates in flexible optoelectronic devices and their functionality was tested in indium tin oxide-free organic light emitting diodes (OLEDs). The PLA substrates were fabricated by extrusion and characterized in terms of morphological, optical and wettability properties. The films showed optical transmittance of about 90% in the visible region and surface roughness of about 12 nm, optical and morphological parameters suitable for OLED applications. Different structures were fabricated on top of the PLA substrates by hybrid technology through solution-based and thermal evaporation deposition methods. Good electro-optical properties were detected in iridium complexes-based devices, with current efficiencies of about 14 and 1 cd/A in structures with tris[2-phenylpyridinato-C2,N]iridium(III) (Ir[ppy] 3 ) and bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium (FIrPic) as emitting layer, respectively. The biocompatibility assay showed that the encapsulated devices do not release toxic substances and their biocompatibility can be improved by selecting different encapsulating glues. The results of this study show the potentiality of PLA as substrate for the fabrication of biocompatible and biodegradable optoelectronic devices opening new routes for the development of advanced bio-electronic systems.