Strobilation is a well-organized metamorphosis process in scyphozoan jellyfish, through which the benthic polyp develops into the pelagic medusa. So far, knowledge on the molecular mechanisms behind the drastic morphological and physiological changes remains limited. In the present study, the metabolic profiles in polyp and strobila stages of jellyfish Rhopilema esculentum were examined using ultra-performance liquid chromatography coupled to a mass spectrometer. A total of 3071 metabolites with putative annotation were detected, of which 167 were identified as differential metabolites between the polyp and strobila. Among the metabolites, 31 significantly decreased and 136 significantly increased in abundance in the strobila. Thyroxin, one of the previously proposed strobilation inducer of Aurelia , was not detected in this study. The indole-containing compounds are known for triggering strobilation in Discomedusae. Two indole derivatives and an indole-isomer containing metabolite were detected among the most significantly increased metabolites, which may be potential endogenous molecules for strobilation initiation. The membrane-associated phospholipids and the inflammation and oxidative stress-related eicosanoids were found to have significant changes. Although the functions of these metabolites in strobilation are not yet completely known, they provide some clues to the induction of the process of strobilation and metabolic responses that take place during strobilation.