<p>Chirality plays a pivotal role in the properties of biologically active molecules, with enantiomers exhibiting divergent pharmacological and toxicological profiles. Enantioselective recognition is thus crucial in drug development, asymmetric synthesis, and environmental monitoring. Luminescence sensing has emerged as a powerful strategy for enantioselective recognition due to its fast response and visual readout capabilities. Covalent-organic frameworks (COFs) offer a promising platform for such applications by combining structural robustness, modular functionality, and inherent porosity. However, achieving both high enantioselectivity and quantitative sensing within a single system remains highly challenging. Herein, we present a cation-induced strategy for enantioselective sensing using a terbium-loaded chiral COF, Tb@CD-COF. Through a facile cation exchange of piperazine cations of CD-COF with Tb³⁺ ions, we revealed a synergistic integration of cation-enhanced luminescence and chiral cavity-based enantioselective recognition mechanism. Tb@CD-COF demonstrates visually discernible colorimetric responses and quantitative enantiomer discrimination, offering a robust and efficient platform for advanced enantioselective sensing applications.</p>