Abstract
(1) Background: Essential oils (EOs) have emerged as promising antibacterial agents due to their broad-spectrum activity and low risk of resistance development. Therefore, this review aimed to assess the effectiveness of EOs against Gram-positive ESKAPE pathogens, and to evaluate their safety and toxicity in mammalian cells. (2) Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science. (3) Results: Heracleum pyrenaicum exhibited the most potent effect, with a MIC of 0.02-0.04 µg/mL and a selectivity index ranging from 251.3 to 2006.5, indicating high selective toxicity toward bacterial cells over mammalian cells. In contrast, certain species such as Cannabis sp. and Citrus sp. had selectivity indices of <1, indicating toxicity to mammalian cells. Ocimum basilicum showed good efficacy against methicillin-resistant S. aureus (MRSA), with a selectivity index of 23.4-34.9, while Satureja nabateorum demonstrated potent activity against E. faecium, with a selectivity index of 65.6-87.2. (4) Conclusions: EOs from Heracleum, Eucalyptus, Cinnamomum, Mentha, Thymus, and Syzygium aromaticum had good efficacy and high safety margins and show a potential for development for treating Gram-positive ESKAPE pathogen infections. However, EOs with a narrow safety margin (selectivity index < 10) raise concerns and warrant further in vivo and clinical trials to better understand their therapeutic windows and potential adverse effects.