In March, it was rumoured that Clooney was pursuing the former "Desperate Housewives" star while they were both in Berlin, even though he was still seeing Keibler at the time.
Longoria took to micro-blogging platform to clear the air, reports femalefirst.co.uk.
"As interesting as the George Clooney rumours are, they aren't true. George and I have been friends for years," she posted.
Clooney and wrestler Keibler went splitsville earlier this month, while Longoria is dating businessman Ernesto Arguello.