Andre Marin says he was spurred to act after reviewing the case of Allan Maki, who was in diabetic shock when he caused a crash that killed three people in Hamilton in 2009.
Marin says the case raises serious questions about how the Transportation Ministry obtains information about drivers with uncontrolled hypoglycemia and what action is taken.
Maki was found guilty of dangerous driving in December 2011 and the ombudsman says family members of the crash victims came to him with the case.
Marin says it took the provincial ministry almost two years after the crash to suspend Maki's licence — even after his case was flagged by police and a physician.
The investigation is expected to take about six months.
Ontario requires medical professionals to report drivers who have uncontrolled hypoglycemia, or low blood sugar, to the ministry so they can be assessed.
The ombudsman's office says an estimated one million people have diabetes in Ontario.
"Although most drivers who have diabetes are perfectly safe, the condition of uncontrolled hypoglycemia was deemed serious enough that Ontario and other provinces made it a reportable condition," Marin said.
"But if that requirement doesn't result in appropriate action by the ministry, it is meaningless. Our investigation will determine whether processes in place are adequate to protect public safety."
He pointed to studies that suggest as many as 25 per cent of those being treated with insulin could experience hypoglycemic unawareness: the inability to recognize the warning signs of low blood sugar and potential impairment.
"I am launching this investigation because this is a potentially systemic problem that could affect the safety everyone who uses our roads," said Marin.