San Buenaventura de Guadalquini was a Spanish mission located on St. Simon's Island, Georgia, United States from before 1609 until 1684, when pirates burned the mission and its town.
Guadalquini was the Timucua language name for St. Simon's Island. It was occupied by members of the Mocama tribe of the Timucua people when Europeans arrived in northeastern Florida and southeastern Georgia in the 16th century. The mission of San Buenaventura was established on the southern end of Guadalquini (St. Simon's) Island at some time between 1597 and 1609. Following increased tensions between Spanish Florida and the English Province of Carolina, and attacks by French pirates on Spanish missions and ranches, the Governor of Florida began plans to withdraw Spanish missions along what is now the coast of Georgia. Shortly after most of the people and their stored food had been moved to the mainland, in 1684, pirates attacked the island and burned the mission church. The people of Guadalquini then moved to a site on the north side of the St. Johns River, where a new mission named Santa Cruz de Guadalquini was established. This mission is also referred to as Santa Cruz y San Buenaventura de Guadalquini. Archaeologists have excavated a site in the Timucuan Ecological and Historic Preserve that may be that mission.