Splashtop does NOT work in safe mode on Windows XP and Windows Server 2003.
Splashtop does work in safe mode for Windows 7 and higher and Windows Server 2008 and higher.
This means the Splashtop streamer can auto-launch in safe mode. If network is available, a remote session can also be established to it.
Update 10/17/2017:
Remote Reboot to normal and safe mode is a feature that has been released since December 2016.