Depending on your setup - disk space and so on, you might consider veracrypt. It can encrypt entire partitions or disks. In use it takes a moment to 'open' the encrypted volume, but once it is open it does all the encryption/decryption on the fly. I believe the only thing that would be unencrypted while it was in use would be what was actually in memory being used at the moment. The encryption seems to be pretty solid and, if you wish, it can even allow the user deniability, i.e. hidden volumes that cannot be identified as encrypted material. If the program being run created temporary buffers on disk those would be encrypted on the fly as long as they were placed within the encrypted portion.
Once the volume is open it is transparent - there is no noticeable delay while the encryption/decryption takes place.
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