Broken Sword 5: The Serpent's Curse is a classical point & click adventure. It abandons 3D graphics and direct control which were used in the two predecessors and returns to the style of the first two games. The only major technical differences are a higher resolution and that the characters are modelled instead of drawn. The game uses an intelligent mouse cursor: a right click on a hotspot results in looking at the item and a left click triggers an item-specific action. Of course this is the main ingredient of the puzzles: collecting items and using them on other items in order to solve problems. On some occasions there are also logic puzzles from a zoomed-in view on an object, e. g. connecting cables of an engine in order to repair the car's horn. Another important part of the game are conversations with the various characters, some of them known from previous instalments. During the course of the game the controlled character switches between George and Nico. A help function supports players who are stuck.

O enredo da história gira em torno da pintura La Maledicció. George Stobbart e Nicole Collard testemunham como um homem mascarado rouba La Maledicció e mata o dono da galeria. Ambos têm suas motivações para resolver o crime, George trabalha para a seguradora da pintura, Nico é repórter e a polícia é incompetente, e assim eles desvendam uma conspiração que está de alguma forma ligada aos Evangelhos Gnósticos.