Piperazine is a nitrogen-containing heterocyclic compound that is commonly used as an intermediate linking group in the structural derivation of compounds. Heterocyclic drugs containing piperazine have many commercial uses in medicine and are also used in pesticides. For example, the piperazine ring is a key structural element of the systemic fungicide Triforine. Piperazine is an attractive option because of its low acute toxicity to mammals, and it has become one of the hotspots of heterocyclic pesticide research in recent years. The pesticidal activity and mechanism of piperazine derivatives have been studied extensively. Herein, a comprehensive review of the research on the pesticidal bioactivity and mechanism of action of piperazine derivatives from 1971 to 2025 is presented. The agriculturally relevant antifungal, insecticidal, anti-plant virus, herbicidal, acaricidal, and antibacterial activities are discussed and the molecular mechanism of action of related piperazine derivatives is summarized. In addition, we also propose the future derivation direction of piperazine structures and look forward to the development of the anti-plant virus and anti-bacterial action mechanisms.