Simple SummaryRabbits are animals sensitive to alimentary disturbances and various spoilage agents, mostly during the weaning period. For this reason, the use of natural feed additives has become an area of research in rabbit nutrition, mainly with a focus on prevention. The “in vivo” administration of bacteriocins/enterocins shows an increasing potential in the prevention/treatment of animals’ diseases. Therefore, our study focused on the preventive potential of the dipeptide enterocin (Ent) A/P against the methicillin-resistant (MR) Staphylococcus epidermidis SE P3/Tr2a strain in rabbit model, determining its effect on the growth performance, phagocytic activity, secretory (s) IgA, and gut microbial composition of rabbits. Ent A/P increased the weight gain of rabbits and its antibacterial effect showed a tendency to stabilize and improve gut microbiota due to reduction of MR staphylococci, total bacteria, and coliforms. The immune-stimulatory effect of Ent A/P was noted due to increased phagocytic activity. Achieved results showed the great potential of Ent A/P application as a feed additive in rabbit nutrition to improve the health and productivity of animals.The present study investigated the effect of the dipeptide enterocin (Ent) A/P on growth, immune response, and intestinal microbiota in rabbits. Eighty-eight rabbits (aged five weeks, M91 meat line, both sexes) were divided into three experimental groups: E (Ent A/P; 50 µL/animal/day for 14 days; between 0–14 days); S (methicillin-resistant Staphylococcus epidermidis SE P3/Tr2a strain; 500 µL/animal/day for 7 days starting at day 14 to day 21); and E + S (Ent A/P between 0–14 days and SE P3/Tr2a strain between 14–21 days) groups, and the control group (C). The additives were administered in drinking water. Administration of Ent A/P lead to an increase in weight gain, reduction of feed conversion; phagocytic activity was stimulated and gut microbiota were optimized due to reduction of coliforms, total bacterial count, and methicillin-resistant staphylococci. Good health and increased weight gain also showed that methicillin-resistant S. epidermidis SE P3/Tr2a strain did not have any pathogenic effect on rabbits’ health status.