The game allows the player to build a school of gladiators and take them into battle against opposing schools in a quest for fame and glory. The plot focuses on several of the main characters and slowly affects the decisions of the group, eventually leading to a final large battle that tests the skills of all members of the school. Upon starting the game, the player can choose between a school in Imperia, home to a strong military mentality and soldiers who consider their northern neighbors uncivilized and bullish, or a school in Nordagh, where witches and woodland beasts dwell, and who in turn detest the Imperials for their desire for greater conquest.

The gladiators have the opportunity to travel through four distinctly different regions on their road to the ultimate championship. Depending on the player's school choice, he or she begins in either the Northern lands of Nordagh (Barbarian school), which has a culture similar to that of 'Nordic' lands, or Imperia (Gladiator school), an Imperial Roman land. Upon completion of these two stages of play one proceeds onto the Windward Steppes, a grasslands region dominated by archers and beasts, reminiscent of the steppes of Asia, followed by the Southern Expanse, a desert region filled with spellcasters, nomadic warriors, and insects. The latter is an area reminiscent of Egypt; the main insects of this region are beetles, which held a high importance in Egyptian mythology, and scorpions, a staple arachnid in any desert region. The conclusion of the game takes place in and around the large central arena of Caltha in the Imperial Region.

As in many role-playing games, players outfit their characters with gear to increase their abilities, and as they win fights, they gain experience which allows them to don new equipment and undertake new quests. Additionally, winning certain hidden or difficult contests allows the players to recruit unique character classes such as yetis, minotaurs, and the undead. Fighting in Gladius follows a turn-based mechanism, but with a twist. There are "swing meters" - like those found in many golf games - that determine the accuracy and effectiveness of strikes. For those who enjoy more traditional turn-based strategy role-playing games, the meters can be disabled in the options menu. This tends to increase the difficulty level and force the player to rely more on sound tactics than nimble fingers.