Carbon and oxygen isotopes of benthic foraminifera are widely used for paleoenvironmental reconstructions. However, large benthic foraminifera (LBF) shells, as the predominant sediment type in coral reef areas, exhibit isotope values influenced by many factors, especially the “vital effect”, which limits their application. Therefore, this study systematically categorizes the main factors contributing to deviations in the carbon and oxygen isotope values of LBF, including symbiotic algae, the calcification process, individual development, and seasonal variation. Furthermore, the mechanisms underlying these factors are thoroughly examined. Additionally, the potential applications of LBF carbon and oxygen isotope indices are analyzed. Despite the influence of vital effects, these indicators can still serve as powerful tools for paleoenvironmental reconstruction in coral reef areas by selecting suitable species, employing micro-area analysis, and integrating these indices with other paleoenvironmental proxies.