State Route 380 (SR 380) is a north–south state highway in the southwestern quadrant of the U.S. state of Ohio. The southern terminus of SR 380 is at its junction with the concurrency of U.S. Route 22 (US 22) and SR 3 nearly 3 miles (4.8 km) northeast of Clarksville. Its northern terminus is in downtown Xenia, following a brief concurrency with US 68, at the signalized intersection where the U.S. route meets US 42.