Here we utilize chemical biology as a tool to manipulate the biological system of a small, but highly venomous to humans, cubozoan jellyfish, Carukia barnesi. We trialled a range of chemical reagents including indole compounds, 9-cis-retinoic acid and lugols solution to induce metamorphosis between the polyp and medusa life stages. An optimum method was determined resulting in a 90% metamorphosis rate to healthy medusa by exposing the polyps to 1 μM of 5-methoxy-2-methylindole for 24 hours. Of note is that chemical exposure time significantly impacts health and metamorphosis rates in this species. We also present a theoretical mechanism for the chemical/biological interactions occurring during metamorphosis. This is a significant methodological advancement which now enables rearing of this animal en mass in aquaria - a world first for this species - which will subsequently supply and facilitate venom research into this understudied jellyfish.