The newspaper's analysis of hundreds of UN contracts granted since the Syrian conflict began in 2011 showed many awarded to companies run by or linked to key regime players who are under EU and US sanctions.
But the United Nations defended its actions, saying they were taken "in accordance with the core humanitarian principles of humanity, neutrality, impartiality and independence."
The Guardian found that two UN agencies had partnered up with the Syria Trust charity, an organisation started and chaired by Assad's wife Asma, spending a total of $8.5 million (7.6 million euros).
It also said the UN had given money to the state-owned fuel supplier, which is under EU sanctions, and to Syria's national blood bank, which is controlled by Assad's defence ministry.
Money also went to the Al-Bustan Association, owned and run by Assad's billionaire cousin Rami Makhlouf, who is Syria's most notorious and powerful tycoon.
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The UN's Food and Agriculture Organisation had given $13.3 million to the Syrian agriculture ministry, which is on the EU sanctions list, the Guardian said.
"These contracts show how the UN operation has quietly secured deals with individuals and companies that have been designated off-limits by Europe and the US," the Guardian said.
Reinoud Leenders, an expert in war studies at King's College London, wrote in the Guardian that the "UN's alleged pragmatism has long given way to troubling proximity to the regime".
But a UN spokesman defended the contracts.
"It is correct that in Syria, the government determines the non-governmental organisations that the UN agencies in Syria are permitted to work with," explained Jens Laerke, from UN humanitarian agency OCHA.
"If agencies in Syria did not accept this, than they would not be able to save so many lives.
"Our activities are governed by the UN charter...this is done in accordance with the core humanitarian principles of humanity, neutrality, impartiality and independence," he added.