Melatonin, a multifunctional phytohormone, has shown antiviral properties in animals and plants, offering a new approach to managing viral infections. In the animal system, melatonin has shown conclusive efficacy against multiple pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by diminishing cytokine storms and viral replication. This chapter highlights the functions of phytomelatonin in suppressing plant virus infections through biochemical and molecular defence mechanisms. Several studies have shown that melatonin treatment can substantially reduce viral replication, movement, spread and symptom severity in crops such as rice, cucumber, cassava, and tobacco. The major defence mechanisms include reactive species signalling, MAPK signalling activation, and overexpression of pathogen-related proteins. Additionally, melatonin crosstalks with phytohormones and regulates secondary metabolites biosynthesis in the infected plants, which leads to induced defence. Studies have also reported the disruption of melatonin biosynthesis during the interaction of viral coat proteins and host transcription factors such as MeRAV1 and MeRAV2. Furthermore, melatonin influences virus-vector interactions by diminishing vector fecundity and attracting vectors to pretreated plants, and this means reducing broad-scale viral transmission. Comparative transcriptomic analysis has also reported that the upregulation of differentially expressed genes is associated with stress mitigation pathways. Although melatonin presents a novel, environment-friendly strategy for plant virus management, more elaborate research is required to standardise its application and evaluate its longstanding impact on crop health.