Acca sellowiana (O. Berg) Burret (Feijoa) is an evergreen shrub, belonging to the Mirtaceae family. The aim of this study was to investigate the micromorphological features of the feijoa fruit peel and to evaluate the phytochemical profile, as well as the antioxidant, cytoprotective, and antimicrobial properties of its essential oil (EO), by several in vitro cell-free and cell-based assays. The micromorphological analysis showed several schizogenic secretory cavities, immediately below the epidermal layer. Forty compounds were identified and quantified by GC-FID and GC-MS analyses. Sesquiterpenes were the most abundant ones (76.89%), followed by monoterpene hydrocarbons (3.26%), and oxygenated monoterpenes (0.34%). The main compounds were γ-Selinene (17.39%), α-Cariophyllene (16.74%), β-Cariophyllene (10.37%), and Germacene D (5.32%). The EO showed a strong and dose-dependent antioxidant, and free-radical scavenging activity. Furthermore, it showed cytoprotective activity on the lymphocytes, that have been pre-treated with 100 μM tert-butyl-hydroperoxide (t-BOOH), as well as a decrease in intracellular reactive oxygen species (ROS), induced by t-BOOH on erythrocytes. A preliminary antimicrobial screening against GRAM+ and GRAM− bacteria, as well as on fungi highlighted that EO showed the best activity against S. aureus and C. albicans (MIC 2.7 mg/mL). In light of these results, feijoa fruit EO could find various applications, especially in the food, nutraceutical, and pharmaceutical fields.