The Palestinians were shot dead during protests along the frontier with Israel, Gaza's health ministry said, according to AFP.
The flare-up is the latest in months of tensions that have ratcheted up fears of a wider conflict between Israel and Palestinian resistance forces.
An Israeli army statement said shots were fired at troops during renewed protests along the Gaza-Israel borders and "in response... aircraft and tanks targeted military targets throughout the Gaza Strip."
It did not say if any Israeli soldiers were hurt in the shooting.
Two Palestinians were killed in a strike east of Khan Yunis in southern Gaza, the health ministry in the enclave said.
A third man was killed by Israeli fire east of Rafah, also in southern Gaza, the ministry said.
The three men were named as Shaban abu Khatar, Mohammed abu Farhana and Mahmoud Qushta.
Israel's military claimed its aircraft and tanks had targeted "eight military posts" belonging to Hamas.
A fourth man named as Mohammed Badwan was later shot dead by Israeli forces during protests along the border, Gaza's health ministry said.