Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as Lactobacillus spp and Akkermansia muciniphila help to regulate healing processes through both ROS-dependent and FPR-dependent mechanisms. In this review, we will discuss the current knowledge and future perspectives concerning the impact of microbiota on wound healing. We will further review available evidence on whether mechanical bowel preparation and the use of specific antibiotics are beneficial or harmful procedures, an ongoing matter of debate. These practices have a profound effect on the gut microbiota composition at the level of both the mucosal and the luminal compartments. Therefore, a key question remains unanswered: should we continue to prepare the gut before surgical intervention? Current knowledge and data do not clearly support the use of one technique or another to avoid complications such as anastomotic leak. There is an urgent need for appropriate interventions with a deep microbiota analysis to investigate both the surgical technical benefits of a proper anastomosis compared with the potential effect of the gut microbes (beneficial vs harmful) on the processes of wound healing and anastomotic leakage reduction.