The global pandemic of SARS-CoV-2 has highlighted the necessity for innovative therapeutic solutions. This research presents a new formulation utilising the metal–organic framework MIL-101(Al)–NH2, which is loaded with hypericin, aimed at addressing viral and bacterial challenges. Hypericin, recognised for its antiviral and antibacterial efficacy, was encapsulated to mitigate its hydrophobicity, improve bioavailability, and utilise its photodynamic characteristics. The MIL-101(Al)–NH2 Hyp complex was synthesised, characterised, and evaluated for its biological applications for the first time. The main objective of this study was to demonstrate the multimodal potential of such a construct, in particular the effect on SARS-CoV-2 protein levels and its interaction with cells. Both in vitro and in vivo experiments demonstrated the effective transport of hypericin to cells that express ACE2 receptors, thereby mimicking mechanisms of viral entry. In addition, hypericin found in the mitochondria showed selective phototoxicity when activated by light, leading to a decrease in the metabolic activity of glioblastoma cells. Importantly, the complex also showed antibacterial efficacy by selectively targeting Gram-positive Staphylococcus epidermidis compared to Gram-negative Escherichia coli under photodynamic therapy (PDT) conditions. To our knowledge, this study was the first to demonstrate the interaction between hypericin, MIL-101(Al)–NH2 and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which inhibits cellular uptake and colocalises with ACE2-expressing cells. Therefore, the dual functionality of the complex – targeting the viral RBD and the antibacterial effect via PDT – emphasises its potential to mitigate complications of viral infections, such as secondary bacterial infections. In summary, these results suggest that MIL-101(Al)–NH2 Hyp is a promising multifunctional therapeutic agent for antiviral and antibacterial applications, potentially contributing to the improvement of COVID-19 treatment protocols and the treatment of co-infections.