Seafood is source of proteins, healthy fats, vitamins, and minerals in the human diet. Notwithstanding these nutritional advantages, seafood may acquire organic lipophilic nonpolar contaminants, including polycyclic aromatic hydrocarbons (PAHs) and heavy metals, from the aquatic environment, hence presenting potential dangers to consumers. In 2019, the most significant oil spill incident occurred on the Brazilian coast, resulting in the poisoning of marine ecosystems and their inhabitants. Consequently, officials and academics worked to evaluate the contamination levels and associated dangers in seafood from the impacted region. This study sought to assess the contamination levels and bioaccessibility of polycyclic aromatic hydrocarbons in oysters from both natural environments and marine farms situated in the Delta of the Parnaiba River, Piauí state. PAH extraction adhered to the EPA-3545A standard, while bioaccessible fractions were obtained utilizing the liquid–liquid extraction method of the EPA-3510C protocol. The identification and quantification of PAHs adhered to the EPA-8270D procedure. The in vitro digestion simulation was conducted using the INFOGEST 2.0 standard protocol. The average concentration of the 39 assessed PAHs was consistent among the samples. The average quantities of PAHs ranged from 0.26 to 47.22 µg kg−1, with the most significant level detected in oysters from the natural environment. Naphthalene, acenaphthene, anthracene, fluorene, chrysene, benzo(b)fluoranthene, and benzo(a)pyrene were identified in the bioaccessible fraction, with respective bioaccessibility values of 11.53%, 19.33%, 7.78%, 48.2%, 11.95%, and 14.41%. Naphthalene was the most prevalent of the measured PAHs. The bioaccessible percentage of the cultivated oyster samples exhibited the lowest potency equivalent amounts of BaP (1.39 µg kg-1) in contrast to oysters from the wild environment (4.0 µg kg-1). The samples did not exceed the maximum limit of 18.0 µg kg-1 set by the National Agency for Sanitary Vigilance and Safety for mollusks, as per the BaP. The oyster from regions impacted by the oil spill is deemed safe for consumption.