Intelligence officers detained Guaido’s "chief of staff", Roberto Marrero, in a predawn raid on his home, where they seized an arms cache and foreign cash, Venezuelan Interior Minister Nestor Reverol said.
The arrest prompted the US to threaten Caracas with "the toughest sanctions" ever, Press TV reported.
In a televised speech, Reverol showed an image of two rifles that were found in Marrero’s place, saying he was “directly responsible for the organization” of criminal groups.
“This citizen was seized with weapons of war and numerous foreign currency in cash,” Reverol said.
Marrero's bodyguard, Luis Paez, was also detained and faced the same charges and a search was on for "identified" collaborators, he added.
Shortly after their detention, President Nicolas Maduro said he would "not be afraid to fight terrorist groups to put them in jail."
Guaido, who heads the defunct National Assembly, pushed the country into a new political crisis in January, when he suddenly declared himself as “interim president” of Venezuela.
He was recognized by the US as well as some of its Latin American and European allies, ignoring the outcome of last year’s election, in which President Maduro emerged victorious.
Guaido cried foul, describing the detention as a “vile, vulgar kidnapping."
“As they cannot arrest the interim president, they are looking to capture those closest to him.”
Guaido himself is accused in Venezuela of trying to foment a US-backed coup d’état against the Maduro government.
The detention also prompted reaction from Washington, which has repeatedly warned Maduro not to touch Guaido and his inner circle.
On Thursday, US Secretary of State Mike Pompeo and National Security adviser John Bolton called for Marrero’s immediate release.
"The United States condemns raids by Maduro's security services and detention of Roberto Marrero, Chief of Staff to Interim President @jguaido,” Pompeo wrote.