Ionic liquids (ILs) attracted global attention owing to their superior functional properties, making them useful for many applications. Low volatility, wide liquidity range, better miscibility with organic and inorganic materials, better electrochemical stability, and negligible toxicity earn them a green solvent status. ILs are suitable alternatives to many volatile and flammable organic solvents that chokes our environment. The presence of asymmetric organic/inorganic ions gave them unique characteristics similar to biomolecules. They could interact with the cell membranes and penetrate the lipid bilayers to destroy bacterial cell membranes. They can selfassemble at the interfaces of polar and non-polar media. The nature of substrates, concentration, counter-ions, and polarity of the medium influence the extent and stability of the self-assembly. The self-assembled monolayers (SAMs) and multilayers of ILs impart intriguing properties to the surfaces. Surface modification with ILs is preferred over other methods considering their eco-friendly nature. The IL-mediated surface modification would help to improve the surface properties of polymers, metals, nanoparticles, ceramics, stones, medical devices, etc. The modified surfaces would have improved wettability, biocompatibility, and antimicrobial or antiviral properties. IL-modified surfaces could anchor enzymes to generate sustainable biocatalysts for a wide range of reactions. The inherent affinity of ILs towards gases like CO2 makes them suitable for generating gas-adsorbing surfaces. Assembled charge carriers in ILs are helpful in energy storage and electrochemical sensing applications. Poly(ionic liquids) (PILs) are also receiving much attention recently since they display synergistic properties of polymers and ILs to be employed in divergent fields. PILs are also suitable for the surface modification of different substrates. This chapter reviews the surface modification of materials using ILs and PILs and their biomedical applications.