In this work, the practical/analytical potential of an L-valinederived polyacetylene (PLA) lyotropic liquid crystal (LLC) is examined to spectrally discriminate enantiomers (racemic mixture) or enantiotopic directions of a large collection (23) of (pro)chiral model compounds (from rigid to flexible and polar to apolar ones), thus covering various important aspects of enantiomorphism. Experimental 2H-{1H} (deuterated analytes and at natural abundance level) and 13C-{1H} NMR results are discussed in terms of the difference of 2H-RQCs or 13C-RCSAs and compared to those obtained in polypeptide-type LLCs (PBLG). The analysis of the NMR results provides an overview of the enantiodifferentiation capabilities of PLA and gives useful/ practical hints for the chemist to select the most appropriate chiral oriented system. Astonishing NAD NMR results wereobtained in the case of one of the simplest, chiral alkanes, 3-methylhexane. From a theoretical viewpoint, the data collected highlight the key molecular factors involved in orientation/discrimination processes, as a basis for optimizing computationalprediction (molecular dynamics simulation), as well asdesigning novel helically chiral polymers as new enantiodiscriminating aligning media. In addition, a new, robust and efficient protocol to synthesize PLA and its enantiomer (PDA) on a large scale and with small polydispersities is proposed.