Persimmon fruit quickly softens after harvest, which limits its industrial value. The hormone melatonin has been reported to delay fruit ripening and softening. However, the effect of melatonin on postharvest persimmon fruit remains inconclusive. In this study, we found 10 μM melatonin treatment delayed the softening of persimmon fruit, accompanying with lower levels of endogenous ethylene and abscisic acid (ABA). Further, transcriptomic and metabolomic analysis were applied to investigate the regulatory mechanism. In total, 6831 differentially expressed genes (DEGs) and 1224 differentially accumulated metabolites (DAMs) were identified. We also investigated the metabolism pathways and regulatory networks incorporating crucial structural genes and TF during persimmon fruit softening. They were involving functions of saccharides, organic acids, ethylene biosynthesis, and ABA biosynthesis. In conclusion, our results indicate that melatonin can delay the biosynthesis of ethylene and ABA during persimmon softening and provide new insights into the regulatory pathways of melatonin-maintained persimmon fruit quality. •Melatonin delayed persimmon fruit softening and suppressed the biosynthesis of endogenous ethylene and abscisic acid.•A total of 6831 DEGs and 1224 DAMs were obtained.•Complex regulatory networks involved in pathways of saccharides and organic acids, ethylene biosynthesis and ABA biosynthesis were constructed.