Endoscopes are ubiquitous in minimally invasive or keyhole surgeries globally. However, frequent removal of endoscopes from the patient's body due to the lens contaminations results in undesirable consequences. Therefore, a cost-effective process chain to fabricate thermoplastic-based endoscope lenses with superior antifouling and optical properties is proposed in this research. Such multifunctional surface response was achieved by lubricant impregnation of nanostructures. Two types of topographies were produced by femtosecond laser processing of metallic molds, especially to produce single-tier laser-induced periodic surface structures (LIPSS) and two-tier multiscale structures (MS). Then, these two LIPSS and MS masters were used to replicate them onto two thermoplastic substrates, namely polycarbonate and cyclic olefin copolymer, by using hot embossing. Finally, the LIPSS and MS surfaces of the replicas were infiltrated by silicone oils to prepare lubricant-impregnated surfaces (LIS). Droplet sliding tests revealed that the durability of the as-prepared LIS improved with the increase of the lubricant viscosity. Moreover, the single-tier LIPSS replicas exhibited longer-lasting lubricant conservation properties than the MS ones. Also, LIPSS-LIS replicas demonstrated an excellent optical transparency, better than the MS-LIS ones, and almost match the performance of the reference polished ones. Furthermore, the LIPSS-LIS treatment led to superior antifouling characteristics, i.e., regarding fogging, blood adhesion, protein adsorption, and microalgae attachment, and thus demonstrated its high suitability for treating endoscopic lenses. Finally, a proof-of-concept LIPSS-LIS treatment of endoscope lenses was conducted that confirmed their superior multifunctional response.