The 1994-born Juventus defender was out-of-favour at the Allianz Stadium last season and he was sent out on loan to Rennes initially and then Cagliari.
He did well in the second half of the season when he returned to Serie A and Tuttomercatoweb is reporting that he has caught the attention of the La Liga side.
Manuel Pellegrini’s club needs a new centre back and they have been on the lookout for one.
They have now targeted Rugani who the report insists is on the list of players that could leave Juventus this summer.
His return will give Massimiliano Allegri too many centre backs to work with and if he stays, he knows he would be behind the likes of Leonardo Bonucci, Giorgio Chiellini and Matthijs de Ligt.
Real Betis finished 6th on the La Liga table last season and will play in the Europa League in the next campaign.