Route 215 is a highway in southern Missouri. Its northern terminus is at Route 39 south of Stockton; its southern terminus is at U.S. Route 65 between Buffalo and Springfield. Except for a short section which overlaps Route 13, it is a two-lane highway its entire length. It was originally a set of supplemental routes. In the early 2000s, US 65 was realigned and the southern terminus was extended about one mile (1.6 km) east opposite the western terminus of Route O. The highway runs more east–west than north–south, but is marked as a north–south highway.

The highway begins three miles (5 km) southwest of Stockton near Stockton Lake. Two miles west (at Umber View Heights), the highway crosses Stockton Lake and enters Stockton State Park. Shortly before reaching Bona, it crosses another arm of Stockton Lake, and at Bona is an intersection with Route 245. East of Bona, it crosses yet another arm of Stockton Lake, then begins a six mile (10 km) concurrency with Route 123. At Eudora, the concurrency ends.

Seventeen miles east of Eudora, the highway joins Route 13 for one mile (1.6 km), then turns east. The highway continues east to US 65 where the highway ends.