In this study, we mainly focused on some in vitro biological activities of a series of (5 or 6)-amino-2- (substituted phenyl and benzyl) benzoxazole derivatives. For this purpose, we tested cytotoxic and genotoxic activities of them on cancer cell lines and their topoisomerase inhibitory activities. We also tested their cytotoxic and genotoxic activities on non-cancerous cells (L929) and their mutagenic activities by Ames test to evaluate their effects on healthy cells. Only TD5 was found cytotoxic on all the tested cancer cell lines and did not exhibit either cytotoxic or genotoxic activities against healthy cells, whereas TD1, TD2, TD3 and TD7 were more cytotoxic against only HeLa cells. Only TD4 was found as mutagenic derivative. None of the compounds had any topoisomerase inhibitory activities nevertheless some of them caused inhibition of topoisomerase II activity. Additionally, we used an in silico model to predict the drug-like properties of them to evaluate their bioavailability to the QikProp Properties Predictions. All the calculated properties were found in a permissible range. According to the data obtained from biological activity studies, it can be concluded that the methylene bridge at the position 2 of benzoxazole ring decreases cytotoxic activity on cancer cells and inhibitory activity on DNA topoisomerases.