A female in her 30s and a male in his 50s are both in a serious but stable condition.
The fifth patient, a male teenager, is in a stable condition.
One helicopter was on the scene at 5.15pm.
One rapid response vehicle and three ambulances were also at the crash.
A Fire and Emergency spokesman said firefighters cut one person from the vehicle.
Traffic management was put in place and the Serious Crash Unit had been notified.
Police remained at the scene until 9.03pm.
A second single-vehicle crash occurred on the road hours later near the intersection of Turangakumu Rd near Te Haroto at 12.55am Monday morning.
Police were called to the scene but there were no reports of injuries or road blocking, a police spokeswoman said.
