In this study, oil spills were simulated in field-based mangrove mesocosms to compare the efficiency of bioremediation strategies and to characterize the presence of the alkB, ndo, assA, and bssA genes and the ecological structures of microbial communities in mangrove sediments at two different depths, (D1) 1–10 cm and (D2) 25–35 cm. The results indicated that the hydrocarbon degradation efficiency was higher in superficial sediment layers, although no differences in the hydrocarbon degradation rates or in the abundances of the alkB and ndo genes were detected among the tested bioremediation strategies at this depth. Samples from the deeper layer exhibited higher abundances of the analyzed genes, except for assA and bssA, which were not detected in our samples. For all of the treatments and depths, the most abundant phyla were Proteobacteria, Firmicutes and Bacteroidetes, with Gammaproteobacteria, Flavobacteriales and Clostridiales being the most common classes. The indicator species analysis (ISA) results showed strong distinctions among microbial taxa in response to different treatments and in the two collection depths. Our results indicated a high efficiency of the monitored natural attenuation (MNA) for oil consumption in the tested mangrove sediments, revealing the potential of this strategy for environmental decontamination and suggesting that environmental and ecological factors may select for specific bacterial populations in distinct niches.