Transient receptor potential vanilloid (TRPV) channels are a member of the TRP superfamily, which consists of six proteins and is expressed in many neuronal and non-neuronal cells. Among them, TRPV1-4 are non-selective cation channels that are highly sensitive to temperature changes, while TRPV5-6 are channels that are highly selective to Ca2+. These cation channels have attracted great interest academically, especially from a pharmacological perspective. TRPV channels play a vital role in many physiological processes and can be regulated by a variety of endogenous stimuli as well as a range of natural and synthetic compounds. The regulation of their activities can lead to a variety of diseases and disorders, such as neurodegenerative diseases, pain, cancer, and skin diseases. In fact, several TRPV1 and TRPV3 modulators have been developed for clinical use. Therefore, the development of TRPV channel modulators has important clinical significance and value. Herein, we focused on and summarized the latest research progress of endogenous and exogenous ligands of six TRPV channels and their pharmacological effects on related diseases.