The US State Department published an advisory on Monday urging potential investors to be wary of "endemic corruption" and a lack of respect for human rights in the country.
It followed an updated travel warning issued by Washington earlier this year after Ugandan President Yoweri Museveni signed into law a draconian anti-gay bill.
"Businesses, organisations, and individuals should be aware of potential financial and reputational risks resulting from endemic corruption," the advisory said.
It also warned of "violence against human rights activists, media members, health workers, members of minority groups, LGBTQI+ persons, and political opponents."
Uganda's adoption of the Anti-Homosexuality Act in May triggered outrage among human rights groups, LGBTQ activists, the United Nations and Western powers.
US President Joe Biden called for the immediate repeal of the measures and threatened to cut aid and investment in Uganda, while the World Bank announced it was suspending new loans to the country.
Uganda ranks 142nd out of 180 countries on Transparency International's Corruption Perceptions Index.
Uganda's junior information minister, Godfrey Kabbyanga, urged US investors to ignore the State Department warning.
"Advisories of such nature are laughable because they do not match what is on the ground," he told AFP.
"This is not the first time our American friends are issuing such negative advisories on Uganda. But Uganda has not collapsed and instead as a country we are moving stronger and stronger."
The US advisory highlighted the anti-gay law as one of the risks of doing business, saying it "increases restrictions on human rights, to include restrictions on freedom of expression, peaceful assembly, and exacerbates issues regarding the respect for leases and employment contracts."
But Kabbyanga dismissed concerns about the legislation, which is among the harshest in the world and contains provisions making "aggravated homosexuality" a capital offence and penalties for consensual same-sex relations of up to life in prison.
The law, he said, was "in the best interest of our country and our people and not for any other country or entities, and Ugandans are happy with it."
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