Eugenia is ranked the second largest genus in family Myrtaceae and its species are distinguished by numerous health and economical significance. The current study aimed to comparatively investigate the anti-inflammatory and antimicrobial activities of the essential oils (EOs) and lipoidal matters (LMs) derived from Eugenia uniflora L. (EU) and Eugenia supraaxillaris Spring ex Mart. (ES) leaves cultivated in Egypt for the first time. The oils were obtained by the hydrodistillation (HD) and supercritical fluid solid-phase micro-extraction (SF-SPME) methods, while the lipoidal matters were extracted using petroleum ether. The GC/MS analysis of HD EO showed that curzerene (39.85%) was the abundant constituent in EU, while germacrene D (16.86%) in ES. The SF-SPME EOs showed that (E)-2-hexenal is a chief component in both species representing 93.87% (EU) and 46.68 % (ES). On the other side, EU LM was pioneered with hydrocarbons (95.26%) and to a lesser extent with sterols (4.08%), while both classes were evenly tracked in the LM of ES. Lastly, lauric (13.74-17.76%) and oleic (4.26-3.57%) were the most identified fatty acids in both species. The results of the bioactivity screening showed that LM of ES demonstrated the best anti-inflammatory activity through inhibiting cyclooxygenase-2 enzyme with IC50 0.13 µL/mL followed by its LM with IC50 0.135 mg/mL, while EU samples showed moderate activity. Likewise, EOs of both species displayed antimicrobial potential on all tested organism with MIC>40 µL/mL, while their LMs displayed moderate activity (MIC≥200 mg/mL). The observed activities may be possibly, at least in part, to the synergism between the individual metabolites of the EOs and LMs. In all, our study endorses the promising potential of the EOs and LMs from both Eugenia species in the management of microbial infection in addition to related inflammatory disorders.