In the present study, 18 new compounds were synthesized, 9 of which were urea (9a-e, 10a-d) while the others were thiourea (11a-e, 12a-d) derivatives. These derivatives were prepared by the reaction of 6-amino-5-nonsubstituted/chloro-3-methyl-2(3H)-benzoxazolones used as key intermediates with the appropriate isocyanates and isothiocyanates. The chemical structures of new compounds were confirmed by H-1-NMR, mass, and elemental analysis. The synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains. Compounds 9a, 9b, 9e, 10a, and 10c, urea derivatives, and compounds 12a and 12d, thiourea derivatives, exhibited a relatively good inhibitory profile against E. coli, with a MIC value of 32 mu g/mL when compared with the other target compounds.