| South Main nocat = yes | |
| Location: | S. Main St., Middletown, Ohio |
| Coordinates: | 39.5125°N -84.4092°W |
| Architecture: | Greek Revival, Italianate, Queen Anne |
| Added: | March 21, 1978 |
| Refnum: | 78002015 |
South Main Street District is a historic district in Middletown, Ohio.
It contains 76 contributing buildings, including single-dwelling, professional, and specialty store uses.
The district was listed in the National Register of Historic Places in 1974. It includes the John B. Tytus House, which is a National Historic Landmark.