Geochemical studies can provide a record of environmental changes and biogeochemical processes in sedimentary systems. Analytical methods are in need of high-throughput procedures targeting recalcitrant and multiple chemical species for delineating ecological patterns and ecosystem health. The goal of this chapter is to summarize the analytical methods, recalcitrant molecules and transformed organic material used in previous studies as chemical indicators of the impact and fate of Deepwater Horizon (DWH) oil residues in sediments. Further monitoring of recalcitrant molecules and transformed material will help to elucidate the long-term fate of the DWH weathered oil in sedimentary environments of the Gulf of Mexico (GoM).