The United States is concerned the deal, thrashed out over 12 years of talks, does nothing to punish Iran over its ballistic missile programme, interference in regional conflicts or human rights abuses at home.
In a statement, Guterres said "issues not directly related to the JCPOA should be addressed without prejudice to preserving the agreement and its accomplishments."
The 2015 nuclear deal, known as the Joint Comprehensive Plan of Action (JCPOA), is a "major achievement of nuclear non-proliferation and diplomacy, and has contributed to regional and international peace and security," he said.
Trump on Friday agreed to waive US nuclear-related sanctions but warned it was the "last chance" to fix the Iran deal, demanding that US lawmakers and European allies fix the "disastrous flaws" of the accord.
Iran has ruled out any change to the deal, which was signed with the US, Britain, France, Germany, China and Russia.
Concerns regarding the implementation of the nuclear deal should be addressed "through the mechanisms established by the agreement", Guterres said in the statement marking two years since the accord went into force.
He noted that the International Atomic Energy Agency (IAEA) has repeatedly confirmed that Iran is fulfilling its nuclear-related commitments under the deal.
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