In this paper, CuInS2@ZnS (CIS@ZnS) core-shell quantum dots (QDs) were applied for the detection of heavy metals and bioanalytes. These Glutathione (GSH) capped CIS@ZnS QDs with an average size of 3.8 nm were treated using different biologically important biomolecule analytes, such as ascorbic acid (AA), citric acid (CA), oxalic acid (OA), cholesterol (Ch), cysteine (Cy), dextrose (Dx) and urea (U). According to spectroscopic analysis, the addition of cholesterol showed photoluminescence (PL) spectra of QDs remains unchanged at the main peak position 600 nm but generates a new peak at 487 nm with cholesterol dependent enhancement. Furthermore, the addition of citric acid contributes to PL quenching in the core-shell QDs without any spectral shift. Likewise, the interaction of CIS@ZnS QDs with different physiologically important heavy metal ions (HMI) was systematically studied as a luminescence probe. It was found out that the PL emission of CIS@ZnS QDs was effectively quenched by copper (Cu2+) ion with significant spectral shift detected. However, Hg2+ ions also lead to PL quenching at nanomolar level but with no spectral shift observed. According to these results, CIS@ZnS QDs are selectively sensitive to cholesterol, citric acid, Cu2+ and Hg2+ ions with satisfactory detection limit at nM level.