In the present paper we describe the biological activity of newly designed and synthesized series of pyrrolo[3,4-c]pyrrole Mannich bases (7a-n). The Mannich bases were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (6a-c) with secondary amines and an excess of formaldehyde solution in C<sub>2</sub>H<sub>5</sub>OH. The chemical structures of the compounds were characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, FT-IR, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 7l. All synthesized derivatives were investigated for their potencies to inhibit COX-1 and COX-2 enzymes by colorimetric inhibitor screening assay. In order to analyse the intermolecular interactions between theligands and cyclooxygenase, experimental data were supported with the results of molecular docking simulations. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2.