The reaction of 3-methylbenzofuran-2-carbohydrazide (1) with l-phenyl-2-bromoethanone (2a) or 2-chloro-1-(4-chlorophenyl)ethanone (2b) afforded (Z)-1,2-di[(3-methylbenzofuran-2-carbohydrazido]-1-arylethenes 5a and 5b, respectively. Single crystal X-ray analyses of compound 5a proved that the reaction proceeds in 2:1 molar ratio and ruled out the other possible structures 1,3,4-oxadiazine derivative 6 or E-isomer 7. Furthermore, both of 3-(3-methylbenzofuran-2-yl)-3-oxopropanenitrile (9) and 3-methyl-2-benzofuranoyl chloride (15) were used as starting materials for the synthesis of several compounds, such as pyrazoles 10 and 14, oxime 11, hydrazones 12a, b and 3,1-bezoxazine 19. The newly synthesized compounds were tested for their antimicrobial activity against five fungal species and four bacterial species also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Some of these compounds exhibited a significant antimicrobial activity.