The bus was going to Bhopal from Indore.
The deceased were identified as Prahlad Singh (35) and Gokul Prasad (40), both residents of Narsinghgarh town in Rajgarh district, Ashta Police Station In-charge B D Beera said.
"After being hit by the bus, the motorcycle was dragged for some distance and later roadside agriculture field where it finally stopped," he said.
The bus passengers suffered minor injuries in the incident.
The mishap led to traffic snarls for some time, but the road was soon cleared, police said.