Oyster reefs are important coastal habitats because they provide ecosystem services such as water filtration, habitat provision, shoreline stabilization, and nutrient retention. The Liyashan oyster reef is located inshore of the Dongzhao Port, Haimen County, Jiangsu Province, and it is a natural intertidal reef. The oyster reef supports abundant species and high fishery production, and it is a major spawning ground for the roughskin sculpin, Trachidermus fasciatus, which is listed as a second-grade state protection animal. However, there is limited information on the ecological status of the natural oyster reef. In this study, we mapped the reef footprint and monitored oyster populations (species, density, biomass, size-frequency, body condition, genetic diversity, and parasite infection) at the Liyashan oyster reef on the basis of field investigations conducted in 2013 and 2014 and compared the metrics to those of farmed oysters. Aerial photos obtained using an unmanned plane indicate that the natural oyster reef is composed of 750 intertidal reef patches, and the area of a patch ranges from 0.98 m² to 16330 m². The total area of the intertidal reef is approximately 0.201 km². However, the aerial footprint of the natural reef has declined by approximately 39% in the past decade because of sedimentation. Mean cover for live oysters was 66%, and mean densities of the oyster Crassostrea sikamea were between 2199 and 2894 ind./m². The percentage of oyster spats with respect to size-frequency distribution was greater in September than in May, showing high recruitment of oyster larvae in the summer. Mean flesh content, condition index, and gonad index of C. sikamea were (32.15±1.80)%, (9.76±0.95)%, and (600±116) mg/g, respectively. These values were significantly lower at the Liyashan natural oyster reef than at nearby aquaculture sites ((36.50±2.34)%, (15.24±1.04)%, and (1013±82) mg/g, respectively) in Xiangshan Bay, Zhejiang Province. Haplotype diversity and nucleotide diversity index of the C. sikamea population at Liyashan were 0.119 and 0.00028, respectively, and were greater than the values observed at the aquaculture sites. The oyster population had been slightly infected by the parasite Haplosporidium nelsoni, and the infection frequency (17.2%) was lower at the natural reef than at the aquaculture sites (47.3%). The natural oyster reef is rapidly degrading because of heavy sedimentation. The oyster population at the reef had lower body condition, greater genetic diversity, and lower gonad index and parasite infections than those at the aquaculture sites. To protect this important biogenic reef, greater restoration efforts should be initiated to promote the oyster population and reef functions by supplementing hard substrates.