He said the US should focus on defeating the so-called Islamic State rather than convincing Syrian President Bashar al-Assad to stand down.
Mrs Clinton has been proposing a no-fly zone over Syria, which some say could lead to conflict with Russian jets.
The Clinton campaign accused Mr Trump of "playing to Americans' fears".
Mr Trump also attacked Republicans for not uniting behind his candidacy.
"If we had party unity, we couldn't lose this election to Hillary Clinton," he told Reuters news agency at Trump National Doral golf resort in Miami, Florida.
