Homalomena aromatica (Spreng.) Schott is a highly aromatic medicinal plant found in Manipur and other parts of Northeast India. Despite its varied traditional medicinal uses, there are limited reports on plant-part-specific toxicological evaluation of the rhizome and leaf ethanol extracts. In vitro toxicological studies may not adequately replicate complex biological interactions such as metabolism and bioavailability. Therefore, this study focused on in vivo evaluation to obtain a comprehensive toxicological profile. This study compared the phytochemical composition of the rhizome and leaf ethanol extracts of H. aromatica from Manipur, India using gas chromatography-mass spectrometry (GC-MS), antioxidant activity using ABTS and DPPH assays and toxicological profile using zebrafish as a model. The GC-MS analysis of Homalomena aromatica rhizome ethanol extract (HAREE) and Homalomena aromatica leaf ethanol extract (HALEE) revealed the presence of 31 and 25 compounds respectively. The rhizome ethanol extract had a terpenoid-rich composition with the major compounds being Linalyl acetate (monoterpenoid), Oplopanonyl acetate (sesquiterpenoid) and (1R,7S,E)-7-Isopropyl4,10-dimethylenecyclodec-5-enol (sesquiterpenoid) while the leaf ethanol extract showed a more diverse chemical composition with 2-Cyclohexen-3-ol-1-one, 2-dodecanoyl- (vinylogous acid), α- Tocopherol-β-D-mannoside (vitamin E glycoside) and n-Hexadecanoic acid (long-chain fatty acid) being the major compounds detected. The rhizome extract showed a higher 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS) and 2,2´-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity than the leaf extract with IC50 values of 51.23 ± 0.10 µg/mL (ABTS) and 248.81 ± 6.23 µg/mL (DPPH) respectively. However, both were less potent than the standard ascorbic acid. In contrast to the antioxidant activity, the leaf ethanol extract was found to have a higher toxic profile as compared to the rhizome ethanol extract with LC50 values estimated to be 198.81 (leaf) and 558.31 µg/mL (rhizome) respectively. This underscores differential distribution of secondary metabolites in the different plant parts. In conclusion, these findings highlight substantial differences between the leaf and rhizome extracts in chemical composition, antioxidant potential and safety profile.