Police made 53 arrests, including three English fans, after supporters clashed before Southampton's Europa League win at Vitesse Arnhem.
Riot police and horses were called to Korenmarkt, the city's bar district, where opposition fans had been drinking together peacefully.
Some onlookers said the incidents came after provocation from supporters of Vitesse's Dutch rivals Feyenoord.
No problems were reported in the Saints fan zone in nearby Jansplaats.
A Southampton spokesperson said: "Southampton Football Club are aware of an incident away from the official fan zone in Arnhem.
"Fifty Dutch fans have been arrested, three English. Visiting fans are being provided with buses to the stadium.
"We are continuing to liaise with local police and will take relevant action against those involved."
Southampton won the game 2-0 thanks to goals from Graziano Pelle and Sadio Mane, securing a 5-0 aggregate victory.