Antibiotics disrupt the delicate balance of bacteria, fungi, and viruses in the human microbiome. Growing evidence indicates a significant relationship between the intestinal microbiome and cellular therapy, which aligns with the established influence of the microbiome on immune responses. When examining the link between cellular therapy and the microbiome, it is essential to understand how disruptions in the microbiome-especially those caused by antibiotics-affect these therapies. Here, we discuss the impact of antibiotics on the intestinal microbiome, cellular therapy outcomes, and associated toxicities, particularly in the context of hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy. Furthermore, we examine the mechanisms through which antibiotics affect cellular therapy, the future implications of this knowledge, and the areas that warrant further investigation.