  Chiral discrimination that is efficient to tiny amounts of chiral substances,
especially at the single-molecule level, is highly demanded. Here, we propose a
single-shot nondestructive quantum sensing method addressing such an issue. Our
scheme consists of two steps. In the first step, the two enantiomers are
prepared in different rotational states via microwave enantio-specific state
transfer. Then, the chiral discrimination is transferred to quantum hypothesis
testing. In the second step, we for the first time introduce a non-destructive
quantum-state detection technique assisted with a microwave resonator to chiral
discrimination, through which the molecular chirality is determined by the sign
of the output signals. Using a typical chiral molecule, 1,2-propanediol, and an
experimentally feasible model based on spherical Fabry-P\'{e}rot cavity, we
show that the molecular chirality of slowly moving enantiopure gaseous samples
with $10^2 - 10^3$ molecules can be highly credibly distinguished in a
single-shot detection. By further trapping chiral molecules, it is promising to
achieve chiral discrimination at the single molecule level by using our
approach.
