The phytotoxicity of herbicides on crops is a major dilemma
in
agricultural production. Fortunately, the emergence of herbicide safeners
is an excellent solution to this challenge, selectively enhancing
the performance of herbicides in controlling weeds while reducing
the phytotoxicity to crops. But owing to their potential toxicity,
only a tiny proportion of safeners are commercially available. Natural
products as safeners have been extensively explored, which are generally
safe to mammals and cause little pollution to the environment. They
are typically endogenous signal molecules or phytohormones, which
are generally difficult to extract and synthesize, and exhibit relatively
lower activity than commercial products. Therefore, it is necessary
to adopt rational design approaches to modify the structure of natural
safeners. This paper reviews the application, safener effects, structural
characteristics, and modifications of natural safeners and provides
insights on the discovery of natural products as potential safeners
in the future.