For multiple compound query there are two options:
1) compounds belong to the same query (e.g: aligned).
In this case you can just combine them into single SDF file and pass as an argument to _ride script
2) "independent" multiple compounds can be passed one by one into separate RIDE searches
$ICMHOME/icm64 _ride templ1.mol /path/to/Enamine/*.molt
$ICMHOME/icm64 _ride templ2.mol /path/to/Enamine/*.molt outout2.sdf <other_ride_options>
Note that staring from 393a you can provide multiple molt file as an input. (For example if you DB is split into multiple chunks like REAL)
For KNIME: We have node MolRIDE which is a KNIME interface to _ride script.