Lichens were some of the earliest colonizers of terrestrial habitats on Earth. They represent a unique symbiont between fungi (mycobionts) and algae and/or cyanobacteria (photobionts). Lichens have been used as a cure for diabetes, coughs, pulmonary tuberculosis, wound healing, and dermatological diseases. The aim of this study is to investigate the in vitro antioxidant and cytotoxic activities of methanol lichen extracts. Fourteen lichen species from Bidoup Nui Ba National Park were identified according to their morphology and anatomical and chemical characteristics. The antioxidant activity of the methanol lichen extracts was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. The results showed that, of the lichens tested, L5 had the highest free radical activity with 50% inhibitory concentration (IC50) of 59.9 ± 4.65 mg mL−1. The methanol extract of L5 also showed the highest total flavonoid and polyphenol contents. In a cytotoxic assay, it was observed that the methanol extract of U38.1 exhibited high cytotoxic effect against MCF-7 cells, with IC50 of 34.27 ± 1.25 mg mL−1. The tested lichen extracts were also found to have slight cytotoxic effect on fibroblasts at screening concentration of 100 µg mL−1. All of the extracts were found to possess different cytotoxic activities against MO-91 cells, with IC50 values ranging from 10.50 ± 1.56 to over 50 mg mL−1. All of the extracts except U38.1 induced normal peripheral blood mononuclear cell (PBMC) proliferation, especially after 48 h of treatment at 25 µg/mL.