Following meetings with senior Turkish officials, Gates told reporters that if Iran was serious about handing over its uranium it would be working with the International Atomic Energy Agency.
"The reality is they've done nothing to assure the international community" or "to stop their progress toward (building) a nuclear weapon," Gates said.
"And therefore various nations need to think about whether it is time for a different tack," he added.
Gates' blunt rebuff comes as the international community is struggling to reach consensus on how to cajole Iran toward abandoning its controversial nuclear program.
The Obama administration has said Iran appears bent on developing nuclear weapons, although Iran claims its nuclear work is peaceful. Iran is thought to have stockpiled more than enough nuclear material to manufacture a single bomb, and more is being made daily.
Administration officials have invited new talks with Iran, but with no sign that Iran wants to do business, the focus has turned to penalties.
In the latest blow to that effort, China has emerged as an obstacle to winning a fourth round of U.N. penalties.
Speaking to reporters from a Turkish hotel that overlooks the nation's Iranian embassy, Gates said he has sought in his discussions with Turkey and other allies to underscore the threat Iran poses to them.
"Iran is the only country in the region that has publicly declared its intent to destroy another country in the region," he said. If Iran proceeds with this program "unrestrained," there is a "real danger of proliferation" that would destabilize region, he added.
Among the topics discussed this week is Turkey's potential role in NATO missile defense systems based in Europe, which U.S. officials say will help blunt the threat from Iran.
