Maryland State Police are investigating the incident, which took place along Route 301 at Short Cut Road just after 11 p.m. ET.
One of the men was pronounced dead at the scene. The second was taken to a local hospital where he was later pronounced dead.
The driver of the minivan was not injured.
All northbound lanes of Route 301 were closed for several hours. The lanes were reopened at around 4:30 a.m.
The identities of the two victims have not yet been released.