"Two Palestinians were hit and injured by an Israeli drone while they were riding on a motorbike east of Khan Yunis," Gaza's Hamas-run health ministry spokesman Ashraf al-Qudra told AFP.
Palestinian security sources described the two as "militants", without saying to which group they belonged.
The Israeli army confirmed the strike in a statement, saying it had "intercepted terrorists during their final preparations to launch rockets towards Israel".
The strike came after three mortar rounds were fired at Israeli troops along the southern border fence, causing no injuries or damage, it said.
In recent weeks, tensions have risen in and around Gaza after a year of relative calm, with five people killed since December 20. Four of the victims were Palestinian and one was Israeli.
More than a dozen Palestinians have also been wounded over the same period by gunfire or in Israeli air raids on targets in the territory.