The ethics of invertebrate research have largely been ignored compared to the consideration of higher order animals, but more recent focus has questioned this trend. Using biohybrid robotic jellyfish as a case study, we examine the ethical considerations of invertebrate work and provide recommendations for future guidelines. This paper starts with an overview of philosophical views of animal ethics, the current state of knowledge for invertebrate pain and nociception, and current ethical guidelines. Next, we delve into the case study and analogous precedents. Specifically, in prior studies, we developed biohybrid robotic jellyfish, which modified live moon jellyfish with microelectronic swim controllers for future applications in ocean monitoring. Although jellyfish possess no central nervous system, pain receptors, or nociceptors, we closely monitored their stress responses, using the precautionary and minimization principles in consideration of the 4Rs: reduction, replacement, refinement, and reproducibility. We also discuss ethical considerations related to our studies and suggest that public opinion of invertebrate research relies heavily on repugnance, including fears of ‘playing God’ or limiting the ‘free will’ of animals. These issues are also examined for prior bioethics cases, such as the RoboRoach, cyborg beetle, ‘microslavery’ of microbes, biohybrid robots incorporating tissues from sea slugs (which are known to possess nociceptors), and other tissue cutting experiments involving soft-bodied invertebrates. However, biohybrid robotic jellyfish pose further ethical questions of potential ecological consequences as ocean monitoring tools, such as the impact of electronic waste in the ocean. To conclude these evaluations, we recommend that publishers require brief ethical statements for invertebrate research, which can include the following: a scientific justification for the research, discussion of the 4Rs, and cost-benefit analysis. We also delineate the need for more research on pain and nociception in invertebrates, which can then be used to revise or validate current research standards. These actions provide a stronger basis for the ethical study of invertebrate species, with implications for individual, species-wide, and ecological impacts on animals, as well as for interdisciplinary studies in science, engineering, and philosophy.