The incident involving a Ford Transit minibus and a Saab car happened at about 22:15 BST on Wednesday.
The woman driver of the minibus and the male driver of the car were taken to Bangor's Ysbyty Gwynedd.
The road reopened in the early hours following an initial investigation, said North Wales Police.
Two people are in hospital with serious injuries following a crash on the A499 near Pwllheli in Gwynedd.