Senkyunolides are a group of phthalide molecules that exist in Umbelliferae plants, with the highest abundance in Ligusticum chuanxiong Hort, a medicinal herb with therapeutic applications in various diseases such as coronary heart disease, migraine, and rheumatism. Modern research has highlighted the anti-inflammatory, analgesic, and cardiovascular-protective properties of senkyunolides. Recently, some novel effects, such as antibacterial, anti-osteoporosis, and anti-fibrosis, have been reported for senkyunolides, indicating their diverse biological activities. In addition, because of its high bioavailability and ability to cross the blood-brain barrier (BBB), particularly exemplified by senkyunolide I (SEI), holds promise for the treatment of brain diseases. Multiple signaling pathways have been related to the pharmacological activities of senkyunolides, such as the toll-like receptor 4/nuclear factor-kappa B (NF-κB) signaling, extracellular signal–regulated kinase (ERK) pathway, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) pathways. Here, we review the research progress on the pharmacokinetics and pharmacological effects of senkyunolides, which are promising candidates for future drug development and have significant clinical value in the treatment of various diseases.