Single-walled carbon nanotubes (SWCNTs) have emerged to be useful tools in molecular recognition in recent years. Due to their well-defined optical properties, SWCNTs offer unique characteristics that most small-molecule sensors lack. For example, SWCNTs exhibit a near-IR (NIR) photoluminescence which makes them great candidates for sensing biomolecules. Typically, the synthesis of SWCNTs yields over 30 distinct tube chiralities, with two-thirds of the mixture comprising semiconducting and the remaining third consisting of quasi-metallic or true-metallic tubes. To add to the mixture’s structural complexity, each chirality that has the same helicity could also have different handedness – species that are enantiomeric in nature. In our lab at NIST, we have recently developed techniques based on aqueous two-phase extraction (ATPE) to separate enantiomers of SWCNTs wrapped with specific DNA sequences. Most of the sensors that have been developed in this field, whether they are coated and dispersed by surfactants or DNA, take advantage of mixtures of various SWCNT helicities to elicit an optical response from interactions of small molecules. However, the responses obtained from each enantiomeric species of SWCNT is largely ignored, or at best, assumed to be similar. In this presentation, we discuss the differences in photoluminescence responses observed when SWCNTs wrapped with various DNA sequences interact with enantiopure small molecules. With this study, we give proof that specific DNA sequences allow for specific optical responses between the mixtures of diastereomeric DNA-SWCNT nanohybrids and single-chirality enriched DNA-SWCNTs, and enantiomeric amino acids. This study is the first proof-of-concept that small chiral molecules interact with chirality enriched DNA-SWCNTs to different extents and give rise to specific optical signatures that could be exploited for future developments of sensing arrays for complex biological mixtures.