Medicinal plants are increasingly being projected as suitable alternative source for the treatment of various diseases. However, toxic effects resulting from therapeutic bismuth compounds are still documented in animals and humans. This study described the genetic effects of five common lichen species and compared their activities on the genotoxicity induced by the colloidal bismuth subcitrate. After the application of colloidal bismuth subcitrate and lichen extracts, separate and together, human whole blood cultures were assessed by sister-chromatid exchange (SCE) and micronucleus tests. According to our results, the frequencies of SCE and micronucleus rate in peripheral lymphocytes were significantly increased by colloidal bismuth subcitrate (at dose 5 mu g/mL) compared with controls. However, lichen extracts had no genotoxic effect. The order of anti-genotoxicity efficacy against colloidal bismuth subcitrate was Pseudevernia furfuracea, Dermotocarpon intestiniforme, Ramalina capitata, Parmelia pulla, respectively. However, Rhizoplaca melanophthalma did not show any effect against colloidal bismuth subcitrate genotoxicity. Present findings showed that the protective roles of lichens studied were dose related. In conclusion, this is the first study report describing the therapeutic potential of lichens against drug genotoxicity in human blood.