Nuclear receptors are a superfamily of transcription factors induced by ligands, also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, marine natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. 55 ligands were discovered from marine natural resources as LXRs/FXR modulators, 18 agonists and 1 antagonists targeting LXRs, while 4 agonists and 32 antagonists targeting FXR. To better understand above reported active natural products targeting LXR/FXR, the docking evaluation of desired natural products targeted LXRs/FXR is comprehensively discussed. Intriguingly, most of ligands fit into the pocket of the LXRs/FXR, especially for oxepinamides H-K (1-4) (Figure 1) obtained from the deep-sea fungus Aspergillus puniceus SCSIO z021 remarkably bind with LXRα. Meanwhile, a series of steroids, conicasterols B-D (5-7) (Figure 1) isolated from Theonella swinhoei, significantly bind with FXR and have been verified as antagonists via various representative assay including SPR. It is believed and prospective that LXRs/FXR modulators from marine sources, especially marine microbial sources, will take a greater proportion in the future.