Karabatic, who was born in the former Yugoslavia, is appearing with 15 other people.
They include his partner Géraldine Pillet, his brother Luka and his partner, Jennifer Priez.
Six ex-players from Karabatic's former team Montpellier are also in the dock. Primoz Prost, Dragan Gajic, Samuel Honrubia, Mladen Bojinovic, Mickael Robin and Issam Tej.
They deny charges of cheating or plotting to cheat which could lead to five years in jail and a 375,000-euro fine.
Prosecutors say bets of more than 100,000 euros were made on the half-time scoreline of a game on 12 May 2012 between Montpellier and Cesson.
Montpellier had already won the French title while Cesson were fighting to avoid relegation.
Karabatic and his associates are accused of cheating in order to boost the kitty for a holiday in Ibiza.
Nikola Karabatic, Gagic and Tej, have denied placing bets.
Lawyers for the other accused say their clients did make bets but not to manipulate the outcome of the match.
The affair blew up four days after the Montpellier v Cesson game.
The Française des jeux - the body which oversees the national lotteries and betting - said that it had stopped allowing bets at midday on 12 May.
Of the 104,887 euros betted on the game, 102,300 were placed on Cesson leading at half-time. It was 15-12 to Cesson at the pause.
The FDJ said it considered the sums abnormal. Usually an average 3,000 euros worth of bets are placed on a game of handball.
A police investigation was started after the FDJ had contacted detectives who had also received an anonymous-tip-off.
The scandal has besmirched Nikola Karabatic's reputation in France.
Considered a giant of the game, he has won two Olympic gold medals with France in 2008 and 2012 and the world championship three times. There have also been three European titles.