The motorcycle was parked near a bus stop and the bomb was detonated remotely when a police bus carrying officers from the city to the nearby Takwara area passed by, Khan said.
All of the dead were locals, and the explosion at the busy stop wounded both civilians and police constables, he said.
A rescue official, Bilal Faizi, said the wounded were moved to a nearby hospital, where three of them were in serious condition.
There was no immediate claim of responsibility from any group, but the suspicion is likely to fall on the Pakistani Taliban, who have stepped up attacks on security forces since 2022. Authorities say the insurgents have become emboldened while living openly in Afghanistan since the Taliban takeover of that country in 2021.
Dera Ismail Khan is located near the former militant stronghold of South Waziristan, a former sanctuary for militants.
Pakistan's army carried out massive operations against militants in tribal regions along the Afghan border after an army-run school was attacked by militants killing more than 150 people, mostly school children, in 2014.
The army years ago announced that it had cleared the region of local and foreign militants. Occasional attacks have continued, however, raising concerns that the local Taliban, known as Tehrik-e-Taliban Pakistan, are regrouping.
The Pakistani Taliban are a separate group but are allies of the Afghan Taliban, who seized power in Afghanistan in 2021 as the U.S. and NATO troops were in the final stages of their pullout.
Also on Friday, at least 14 soldiers were killed when the military convoy they were traveling in came under attack in the southwest Pakistani town of Pasni, in Baluchistan province.
The military’s media wing said a clearing operation was being carried out in the area and the perpetrators of “this heinous act will be hunted down (and) brought to justice.”