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Metal–organic frameworks (MOFs) can be used as reservoirs of metal ions with relevant antibacterial effects. Here, two novel Zn-based MOFs with the formulas [Zn₄(μ₄-O)(μ-FA)L₂] (GR-MOF-8) and [Zn₄(μ₄-O)L₂(H₂O)] (GR-MOF-9) (H₃L: 5-((4-carboxyphenyl)ethynyl) in isophthalic acid and FA (formate anion) were solvothermally synthetized and fully characterized. The antibacterial activity of GR-MOF-8 and 9 was investigated against <i>Staphylococcus aureus</i> (SA) and <i>Escherichia Coli</i> (<i>EC</i>) by the agar diffusion method. Both bacteria are among the most relevant human and animal pathogens, causing a wide variety of infections, and are often related with the development of antimicrobial resistances. While both Zn-based materials exhibited antibacterial activity against both strains, GR-MOF-8 showed the highest inhibitory action, likely due to a more progressive Zn release under the tested experimental conditions. This is particularly evidenced in the inhibition of <i>SA</i>, with an increasing effect of GR-MOF-8 with time, which is of great significance to ensure the disappearance of the microorganism.