Ganoderma lucidum (GL) is a mushroom used as a traditional remedy for the treatment of various infections since ancient times. This study, was aimed to investigate antimicrobial activity potential of GL against Staphylococcus aureus, Enterococcus faecalis, Listeria monocytogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Candida glabrata, Candida krusei, and Candida parapsilopsis. Furthermore, it was also aimed to evaluate the toxicity potential of GL. Antimicrobial activities were screened by using microbroth dilution method. With regard to toxicity studies, cytotoxicity was evaluated by using XTT method against NIH3T3 cell lines, whereas genotoxicity study was conducted by Ames MPF 98/100 mutagenicity assay. Obtained data indicated that minimal inhibitory concentration values of the extract against the tested microorganisms ranged from 200 to 400 mu g/ml. No cytotoxic activity was observed related to the Ganoderma lucidum administrations. However, results of the Ames test pointed out a genetic damage with metabolic activation against TA98. At the highest concentration (5mg/ml) the extract showed 2.71 fold increase over the baseline significantly. (p<0.05). In conclusion, in spite of significant antimicrobial effect potential, Ganoderma lucidum should be used carefully because of its genotoxicity potential.