Lichens are symbiotic organisms resulting from the mutualistic interaction between a fungus, an alga, and/or a cyanobacterium, along with an associated microbiome, which has enabled their adaptation to various ecosystems across the planet. Throughout this process, they have developed secondary metabolites with a broad spectrum of biological activities. This study explores the potential of bioactive compounds found in Antarctic lichens as antimicrobial agents. Ethanol extracts from species belonging to the genera Cladonia, Gondwania, Himantormia, Lecania, Ochrolechia, Placopsis, Pseudephebe, Psoroma, Sphaerophorus, and Umbilicaria have revealed aromatic compounds from the depside, depsidone, and dibenzofuran groups with variable and significant ranges of antioxidant activity (DPPH IC₅₀ 75.3 ± 0.02 - 2246.149 ± 0.086 µg/mL; ORAC 18.882 ± 0.210 – 525.11 ± 0.135 µmol Trolox/g) and enzymatic inhibition (acetylcholinesterase IC₅₀ 2.805 ± 0.07 – 32.880 ± 0.016 µg/mL; butyrylcholinesterase IC₅₀ 4.476 ± 0.06 – 57.925 ± 0.030 µg/mL; α-glucosidase IC₅₀ 16 ± 0.015 – 250.443 ± 0.006 µg/mL; tyrosinase IC₅₀ 22.32 ± 0.21 - 68.436 ± 0.048 µg/mL), suggesting their potential for antimicrobial research. Additionally, various studies have demonstrated the antimicrobial activity of extracts and isolated compounds from lichens such as Cetraria aculeata, Cladonia rangiferina, Parmelia sulcata, Parmotrema dilatatum, Stereocaulon alpinum, and Usnea barbata against pathogenic bacteria including Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, Enterococcus faecalis, Listeria monocytogenes, and Streptococcus pneumonia, with minimum inhibitory concentrations (MICs) varying between 0.2 and 8.5 mg/mL. The identified mechanisms of action include the inhibition of nucleic acid and protein synthesis, the disruption of cellular integrity, enzymatic activity inhibition, oxidative stress induction, and biofilm formation inhibition. The compounds present in Antarctic lichens represent a promising and innovative therapeutic alternative for combating bacterial infections. However, further in vitro and in vivo studies are essential to validate their safety and efficacy within the context of increasing antimicrobial resistance.