Aim. Elaboration of effective methods for the synthesis of the polysubstituted oximes with the O-acyloxime groups and investigation of their antibacterial and antifungal activity. Methods. organic synthesis, analytical and spectral methods, pharmaceutical screening. Results. A series of new O-acyloximes of 4-formylpyrroles has been synthesized, and the screening of their antibacterial and antifungal activity was performed. It was found that the synthesized compounds exhibit antimicrobial activity, and their minimum inhibitory concentration (MIC) is ranged between 7.81 and 125 μg/mL. A comparatively high antibacterial activity has been registered for some synthesized compounds against the gram-negative bacteria of the genus Proteus (MIC=7.8–62.5 μg/mL). Conclusions. The most active antibacterial O-acyloximes were identified among the array of the synthesized substances, and the MIC of the compound 10 consisting of an m-nitrobenzoilic fragment against the bacterial test strains Proteus aeruginosa ATCC 27853 and Proteus mirabilis ATCC 410 was 15.625 μg/mL. In the case of the latter strain, this value is close to the MIC value of the control drug. The MIC of the compound 9 against the bacterial strain Proteus mirabilis ATCC 410 was 7.81 μg/mL, which is greater than the corresponding control MIC.