Thiosemicarbazones have a wide range of pharmacological applications as anticancer, antiviral antifungal and antimicrobial agents [1]. Many thiosemicarbazones, such as marboran or triapine, are already used in medical practice in clinical trials [2]. Generally, biological activity of thiosemicarbazones increase considerably as a result of coordination to transition metal ions [3]. Copper(II) complexes with thiosemicarbazones display high antineoplastic activity against a large number of various tumours [4]. Bismuth(III) compounds have various applications, especially in the antimicrobial field, due to the local antiseptic, astringent, protective, antacid, antisecretory and gastrointestinal properties. Bismuth(III) compounds are also used in dressings as an antiseptic for application to the skin and for infections of the mouth and upper respiratory tract. Particular emphasis has recently been placed on the use of bismuth compounds in the treatment of duodenal ulcers, peptic diseases and the eradication of Helicobacter pylori [5]. The research is focuses on the synthesis and investigation of the biological activity of homometallic compounds of Cu(II) and Bi(III) with 2-acetylpyridine thiosemicarbazone (HAcpytsc) and 2acetylpyridine 4-ethylthiosemicarbazone (4Et-HAcpytsc) with the general formulas [{Cu(4XAcpytsc)}2Cu(edta)]·nH2O and [Bi(Hedta)(4XHAcpytsc)m]·nH2O (n = 1 - 7; m = 1 or 2; edta4= ethylenediaminetetraacetate; X = H or C2H5) with the monodeprotonated (4XAcpytsc) or nondeprotonated (4XHAcpysc) 2-acetylpyridine thiosemicarbazone or 4-ethylthiosemicarbazones. Ethylenediaminetetraacetate ions were used as chelates with high coordination potential capable to combine two different metals ions and having the ability to amplify the solubility of complexes in water. Aiming at obtaining synergistic effects due to the presence of two biologically active metal ions and different ligands, heterometallic coordination compounds with the same organic compounds were also synthesized. Thus, a series of heterometallic Cu(II)-Bi(III) complexes with mixed ligands were synthesized having the general formulas [{Cu(4XAcpytsc)}Bi(edta)]·nH2O (n = 3 - 5; X = H or C2H5), where both thiosemicarbazones are in monodeprotonated forms. Both homometallic and heterometallic coordination compounds were tested against three bacterial strains: Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Acinetobacter baumannii (BAA-747) and against Candida albicans (ATCC 10231) fungal strain. The results demonstrated that MIC and MBC values for Cu(II) homometallic compounds are in 7,8-0,24 g/mL range, Bi(III) homometallic compounds have the values 7,8- 0,98 g/mL, while the heterometallic compounds have MIC and MBC values in 15-0,061 g/mL domain. The highest antimicrobial activity (0,061 g/mL) was displayed by Cu(II)-Bi(III) heterometallic compound based on 2-acetylpyridine 4-ethylthiosemicarbazone, followed by its Cu(II) homometallic analogue (0,24 g/mL). The synthesized compounds have antifungal activity with MIC and MFC in 62 - 0,98 g/mL range. The highest activity (0,98 g/mL) against Candida albicans (ATCC 10231) has Cu(II) homometallic compound based on 2-acetylpyridine 4-ethylthiosemicarbazone.