Maldives Foreign Minister Ahmed Shaheed has resigned, the country's third cabinet member to do so this month.
President Gayoom has been in power for 29 years
Mr Shaheed, seen as a reformer, accused "conservative elements" in parliament and government of stalling on plans to introduce democracy in the country.
He said he was leaving before a motion of no confidence in him, tabled after he said parliament had failed people.
His move comes two days after President Gayoom claimed victory in a referendum backing a powerful presidential system.
Mr Shaheed is a key architect of the reforms which President Gayoom promised in 2004 after repeated criticism of the Maldives record on human rights.
"There is a conservative guard within the parliament and cabinet which is resisting the proposals of reformists like me," Mr Shaheed told Reuters news agency.
"So I think the answer is to work outside the system and find a middle ground and provide an alternative."
A spokesman for the president said he expected Mr Shaheed to remain a political adviser to Mr Gayoom.
Mr Shaheed's departure comes after the justice minister and attorney general quit earlier this month.
Unlike them, Mr Shaheed did not criticise the president. They had accused Mr Gayoom of delaying reforms.
Mr Gayoom has been in power in the Maldives for the past 29 years.
His party said Sunday's referendum was clear backing for a presidential rather than a parliamentary system of government. The opposition said they suspected the vote was rigged.
The Maldives will hold its first multi-party elections next year.