Daya Bay has been greatly influenced by a variety of human disturbances over the last three decades. Because no extremely useful single biotic index for the assessment of ecological status exists, several biotic indices (the AZTI’s marine biotic index (AMBI), the multivariate AZTI’s marine biotic index (M-AMBI), and the taxonomic diversity (TD) index) were applied to more accurately evaluate the current benthic ecological status of the bay. The results showed that the inner-bay was the most polluted region due to the presence of excess nutrients and pollution associated with anthropogenic activities, while other stations appeared to be in better ecological condition. Temporally, the lower dissolved oxygen concentration in the bottom water might be the main factor leading to worse pollution in autumn. The performance of M-AMBI was better than that of the AMBI and TD indices, and the AMBI and TD indices complemented the M-AMBI in some respects. The results of this study support the use of the AMBI, M-AMBI and TD indices and indicate that these indices may be suitable for assessing the benthic ecological status of semi-enclosed bays under conditions of human disturbance.