"I have every bit of confidence he's going to get himself right with moving himself from the business guy that he is to the president he's going to be," Ryan told CNBC's "Squawk Box."
Concerns about mixing business and politics have tracked the billionaire developer since his election last month. Trump has businesses and real estate holdings around the globe, and he has seemingly admitted to discussing a business-related topic with a foreign official since his presidential win.
The president has some protections under conflict of interest laws, and Trump has contended that "the president can't have a conflict of interest." Still, legal experts and Democrats have consistently raised concerns about the Trump family using the White House to enrich themselves.
Trump next week plans to detail how he will separate from his businesses. Trump has indicated his three eldest children will run his companies, but that may not resolve conflicts as they serve on his transition team. Daughter Ivanka sat in on a meeting with Japanese Prime Minister Shinzo Abe shortly after the election.
Ryan said the "legal details of how he divorces himself from his business" do not concern him in Congress.
"I know he will" cut himself off from his companies, Ryan said.
The Wisconsin Republican said he instead plans to focus on legislation for tax reform, Affordable Care Act repeal and other issues when Trump takes office in January.