Can I use a FloodStop unit on the main water supply to my house?

Sure! If your main water supply is either 3/4 inch, 1 inch, or 1-1/4 inch, then you could use the "FloodStop for Water Heater" in the appropriate size on your main water supply. You may want to purchase some additional sensors to put in various places to the FloodStop unit. See above two questions for more info on extending water sensor coverage.