The protesters on Thursday targeted Prime Minister Recep Tayyip Erdogan, who spoke at the opening ceremony for the games which run to June 30. The games take place every four years among countries of the Mediterranean Basin.
Four demonstrators and two police officers were injured in the skirmishes in Mersin, the private Dogan news agency said. Roads leading to the stadium were closed and barricaded, and protesters kept 10 kilometres (6 miles) from the venue.
Turkey has been hit by sometimes violent protests since May 31, following a crackdown on environmental activists who opposed plans to remove trees and develop Istanbul's Gezi Park.
Serkan Baltaci, deputy co-ordinator of the country's International Relations Department, said the ceremony which was attended by IOC President Jacques Rogge was not impacted by the protests. He called the protests, which he estimated to number about 150, was "a normal situation" that was typical in a "democratic country."
The event, which takes places every four years, is seen as a dress rehearsal for Istanbul's 2020 Olympic bid. Istanbul is up against bids from Tokyo and Madrid, and has been put on the defensive by the unrest in Turkey, the biggest challenge to the 10-year rule of Erdogan.
Rogge complimented the Mediterranean Games for organizing the event in 18 months, acknowledging the games will have an impact on Istanbul's Olympic bid.
"Well, good games have a good effect definitely and bad games have a bad effect," Rogge said. "So yes of course it has an effect. People are watching what's happening here."
In his opening remarks, Erdogan also said Istanbul's bid would be on the mind of many as they watch the games in Mersin, which is about 1,000 kilometres (621 miles) southeast of Istanbul.
"What we are doing in Mersin is a rehearsal," Erdogan said. "We are preparing for the 2020 Istanbul Olympics. I hope and I wish that many of our athlete friends here, our athlete brothers from 24 countries can be our guests too in Istanbul in 2020. I believe that all of our friends will support us for 2020."