Abstract: Labiatae, a family of the dicotyledonous plants, has attracted extensive interest because of its wide application in foods, drugs and cosmetics. According to the National Census of Chinese Medicine Resources, Labiatae contains about dozens of medicinal plants with multiple pharmacological effects. As part of symbiosis with the host, gut microbiota is closely associated with host health, nutrition, and adaptability. Currently, several studies have revealed the molecular mechanism of Labiatae but only small part of them show the potential effect of the gut microbiota. In addition, most studies just concentrate on the regulation effect of traditional Chinese medicine (TCM) on gut microbiota. This unilateral study ignores the metabolic transformation role of gut microbiome on herb medicines, resulting in the lack of understanding of drug efficacy and pharmacological mechanism. This review, therefore, comprehensively and systematically summarized the active compounds and pharmacological effects of Labiatae, includingSalvia miltiorrhizaBunge,Scutellaria baicalensisGeorgi, andPerilla frutescens(L.) Britt, and revealed the interaction between those TCMs with gut microbiota, thus promoting a further understanding of the efficacy and pharmacological mechanism of TCM. In the future study, Labiatae can be used as a prebiotic to modulate the structure and composition of gut microbiome to improve the human health status.