The present review is aimed at providing a comprehensive summary of the botanical characteristics, ethnomedicinal uses, phytochemical, pharmacological, and toxicological studies of the genus Ajuga L. The extensive literature survey revealed Ajuga L. species to be a group of important medicinal plants used for the ethnomedical treatment of rheumatism, fever, gout, sclerosis, analgesia, inflammation, hypertension, hyperglycemia, joint pain, palsy, amenorrhea, etc., although only a few reports address the clinical use and toxicity of these plants. Currently, more than 280 chemical constituents have been isolated and characterized from these plants. Among these constituents, neo-clerodane diterpenes and diterpenoids, phytoecdysteroids, flavonoids, and iridoids are the major bioactive compounds, possessing wide-reaching biological activities both in vivo and in vitro, including anti-inflammatory, antinociceptive, antitumor, anti-oxidant, antidiabetic, antimicrobial, antifeedant, antidiarrhoeal, hypolipidemic, diuretic, hypoglycaemic, immunomodulatory, vasorelaxant, larvicidal, antimutagenic, and neuroprotective activity. This review is aimed at summarizing the current knowledge of the ethnomedicinal uses, phytochemistry, biological activities, and toxicities of the genus Ajuga L. to reveal its therapeutic potentials, offering opportunities for future researches. Therefore, more focus should be paid to gathering information about their toxicology data, quality-control measures, and the clinical application of the bioactive ingredients from Ajuga L. species.