Chirality-induced spin selectivity (CISS) is an effect that has recently attracted a great deal of attention in chiral chemistry and remains to be understood. In the CISS effect, electrons passing through chiral molecules acquire a large degree of spin polarization. In this work, we study the case of atomically thin chiral crystals created by van der Waals assembly. We show that this effect can be very large in systems containing just two monolayers, provided they are spin-orbit coupled. Its origin stems from the combined effects of structural chirality and spin-flipping spin-orbit coupling. We present detailed calculations for twisted homobilayer transition metal dichalcogenides, showing that the chirality-induced spin polarization can be giant, e.g., easily exceeding 50 % for MoTe 2 . Our results clearly indicate that twisted quantum materials can operate as a fully tunable platform for the study and control of the CISS effect in condensed matter physics and chiral chemistry.