This pioneering study examined the wound healing and regeneration abilities of the upside-down jellyfish Cassiopea at the Cnidarian Laboratory of the ICAR-Tuticorin Regional Station, Central Marine Fisheries Research Institute (CMFRI), India. A total of nine specimens (5.8 ± 0.4 cm) were studied, including six control medusae, one accidentally injured jellyfish (cut into four unequal fragments), and two amputated jellyfish (each divided into four equal fragments, totalling eight fragments). All specimens were maintained in a recirculatory aquarium system under optimal seawater conditions. Species identification of the control was confirmed through Basic Local Alingment Search Tool (BLAST) analysis of the 16S rRNA gene, showing 98.91% similarity with Cassiopea xamachana (Bigelow 1892), from the United States of America (USA) GenBank Accession No. ON545804.1, and validated through phylogenetic analysis. Microscopic and morphological observations revealed that the oral arm tissue lacked pulsing activity and could not regenerate its body structure. In contrast, fragments of umbrella tissue from both amputated and injured specimens exhibited pulsing and successfully regained symmetry within 7–15 days. The first phase of self-healing involved the reformation of umbrella symmetry, regeneration of bell tissue, and resumed functions similar to those of the normal medusa. The development of canal systems, including anastomosing vessels radiating from the centre, oral arms extending from the mouth, vesicles from the arms, and the central disc, was documented. The experimental observations revealed sequential wound healing through regeneration and morphogenesis in amputated and injured medusa. This study established Cassiopea as a promising cnidarian model organism for regeneration studies, highlighting its remarkable self-repairing and regenerative capabilities.