A police spokesman said emergency services were called to the single vehicle crash in Fruitlands-Roxburgh Rd (State Highway 8), near the intersection with Waikaia Bush Rd, about 3.10pm.
A Hato Hone St John spokeswoman said one patient was airlifted to Dunedin Hospital in a critical condition.
A rescue helicopter could be seen at the accident site.
The road was closed but reopened about 5.30pm.
A Fire and Emergency New Zealand spokesman said the crash happened near Shingle Creek.
Two appliances and a support vehicle attended from Alexandra and Roxburgh stations.
The one person who was involved in the crash had been heavily entrapped and was extracted by firefighters.
Firefighters also cleared a landing zone for a rescue helicopter, the spokesman said.
