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Melatonin, a trace efficient natural plant signaling molecule, has been widely reported in plant growth and development, abiotic stress, and postharvest preservation and other aspects. In recent years, melatonin has been found to play a positive role in inducing disease resistance in fruits. This paper describes the effect of melatonin on pathogens in vitro and in infected fruits, with a focus on the mechanism by which melatonin induces fruit resistance to invasive diseases. Furthermore, this paper reveals that melatonin and plant signal transduction pathways constitute a regulation network to mediate disease resistance responses in fruits. We conclude this paper with an outlook on future research directions in order to provide a theoretical reference for further research on the mechanism by which melatonin induces disease resistance.