Introduction: Oyster farming is a significant industry worldwide, but it is threatened by various diseases such as Pacific Oyster Mortality Syndrome or vibriosis. V. aestuarianus is a major cause of mortality for market-size oysters, resulting in significant economic losses for oyster farmers. Among the various control methods developed, probiotics appear to be a promising approach. More specifically, the use of the antibacterial activity of bacteria from the natural microbiota of the oyster Magallana gigas appears to be a sustainable solution against V. aestuarianus infections.Results: Our study investigated the probiotic potential of bacteria isolated from the microbiota of M. gigas oysters. We screened a collection of 334 bacteria against eight target pathogens, including V. aestuarianus, and identified 78 bacteria with antibacterial activity for which eight retained this activity in their culture supernatants. Five strains were selected for further testing and exposed to oysters prior to V. aestuarianus infection. Our results show that four strains significantly reduced oyster mortality, with a maximum reduction of 70%. In addition, changes in oyster microbiota composition were observed following exposure, but the administered bacteria were not detected in the microbiota.Conclusion: Our findings demonstrate the potential of oyster microbiota-derived bacteria as probiotics for disease control in oyster farming. This approach could provide a sustainable and environmentally friendly solution for the oyster farming industry. Further research is needed to understand the underlying mechanisms and to develop effective probiotic-based strategies for preventing V. aestuarianus infection.