Core/shell quantum dots (QDs) are of high scientific and technological importance as these nanomaterials have found a number of valuable applications. In this paper, we have investigated the dependence of optical activity and photoluminescence upon CdS shell thickness in a range of core-shell structured CdSe/CdS QDs capped with chiral ligands. For our study, five samples of CdSe/CdS were synthesized utilizing successive ion layer adsorption and reaction to vary the thickness of the CdS shell from 0.5 to 2 nm, upon a 2.8 nm diameter CdSe core. Following this, a ligand exchange of the original aliphatic ligands with l- and d-cysteine was carried out, inducing a chiroptical response in these nanostructures. The samples were then characterized using circular dichroism, photoluminescent spectroscopy, and fluorescence lifetime spectroscopy. It has been found that the induced chiroptical response was inversely proportional to the CdS shell thickness and showed a distinct evolution in signal, whereas the photoluminescence of our samples showed a direct relationship to shell thickness. In addition, a detailed study of the influence of annealing time on the optical activity and photoluminescence quantum yield was performed. From our work, we have been able to clearly illustrate the approach and strategies that must be used when designing optimal photoluminescent optically active CdSe/CdS core-shell QDs.