The protest was held in Gardez, the capital of Paktia Province. Protesters chanted slogans against the US for killing civilians.
The demonstration followed the killing of seven civilians in a US-led strike in the volatile region.
Sources say the protest in eastern Afghanistan turned violent, leaving at least six people wounded.
NATO blames the deaths on bad targeting and communication errors.
Meanwhile, 15 more civilians, including children, were killed when a bomb hit a pick-up truck in the southern Helmand Province.
Civilians have been the main victims of violence in Afghanistan, particularly in the country’s troubled southern and eastern provinces.
According to official figures, more than 2,500 civilians were killed in NATO operations last year, undermining support for the presence of US-led forces in the country.
A recent UN report shows civilian deaths have jumped by 31 percent in the first half of 2010.
Hundreds of civilians have lost their lives in US-led airstrikes or ground operations in different parts of the war-ravaged country over the past months.
The loss of civilian lives has dramatically reduced support for the Afghan war.
The invasion of Afghanistan was launched with the official objective of curbing militancy and bringing peace and stability to the country. Nine years on, however, Afghanistan remains unstable and civilians continue to pay the price.