Reguilon will fill the void left by the knee injury that ruled out Brentford left-back Rico Henry for the rest of the campaign.
The Spaniard spent the first half of this season on loan at Manchester United.
Reguilon made 12 appearances for United but returned to Tottenham this month after Erik ten Hag's side decided to activate a break clause in the deal.
"This is a very good signing for us. We've been talking for a while about how we need a good left-back and we managed to get a very good left-back," Brentford boss Thomas Frank said.
"Sergio is a perfect fit for us: a proven Premier League player in every aspect. He fits what we want. He's very offensive, has a very good cross and a very good left foot.
"He's got the experience we need to complement the rest of the squad and he's a good character.
"We need him, but I also think he needs us to show how good a footballer he is. I'm convinced that this will be a positive partnership."
