Chiral plasmonic nanoparticles (and their assemblies) interact with biomolecules in a variety of different ways, resulting in distinct optical signatures when probed using circular dichroism spectroscopy. These systems show promise for biosensing applications and offer several advantages over achiral plasmonic systems. Arguably, the most notable advantage is that chiral nanoparticles can differentiate between molecular enantiomers and can, therefore, act as sensors for enantiomeric purity. Furthermore, chiral nanoparticles can couple more effectively to chiral biomolecules in biological systems if they have a matching handedness, improving their effectiveness as biomedical agents. In this article, we review the different types of interactions that occur between chiral plasmonic nanoparticle systems and biomolecules, discuss how circular dichroism spectroscopy can probe these interactions, and inform how to optimize systems for biosensing and biomedical applications.