The crash on State Highway 82 happened about 3.45pm and involved only the van.
It appeared the driver had veered to the left and the van left the road, crashed into a ditch then rolled through a fence, ending up back on its wheels in Waihuna Rd.
Sergeant Mike van der Heyden, of Waimate, said the cause of the crash was being investigated
but he believed alcohol or speed could be ruled out.
Other factors, such as fatigue or distraction, would be investigated.
Three Taiwanese tourists and the driver received a range of moderate-to-serious head, arm, neck and other injuries.
Two Otago rescue helicopters were called out and took the four most seriously injured to Dunedin Hospital.
Four ambulances from Oamaru, Waimate and Timaru also attended, one of which took the two patients with minor injuries to Timaru Hospital.
Crash-rescue units and a tanker from the Glenavy and Waimate fire brigades were also at the scene. Sgt van der Hayden said the van was travelling east from Hakataramea when it crashed.
No-one saw the crash, but Taiwanese friends in a rental van were following and came across the injured.
SH82 was reduced to one lane while emergency services helped the injured and prepared them for transport to hospital.
