"No, this is it, it's my last run," said the 63-year-old, who has ruled the tiny Horn of Africa country since 1999 and is widely expected to win a third term on Friday.
His only rival in a poll boycotted by the main opposition parties is a former head of the constitutional council who is running as an independent.
Last year, Guelleh had parliament amend the constitution to allow him to seek another term, sparking an opposition outcry and fuelling unprecedented demonstrations in February.
Guelleh's election rival, Mohamed Warsama Ragueh, is not considered a serious threat but has nevertheless been endorsed by a senior opposition figure.
"If there's an opposition coalition backing the independent candidate, it is in no way a threat to me. On the contrary, it strengthens democracy in our country," he told reporters.
"Since 1999, the opposition has been unable to find a leader and a social programme that are convincing to Djiboutians. The only thing they're good at is insulting me," Guelleh added.
About 150 000 people are eligible to vote out of some 860 000 inhabitants, more than half of whom live in the capital.
The winner will get five years at the head of a largely desert country whose small size belies its strategic importance.
Situated on one of the world's busiest shipping routes where the Red Sea joins the Gulf of Aden, Djibouti hosts the only US military base in Africa and the largest overseas French army base.