Tetracyclines are a family of antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative bacteria, which act as depressants of protein synthesis. Their excellent antibacterial properties and low toxicity make them It is one of the most widely used antibiotics in the world, both in clinical medicine and prophylaxis and in animal feed supplementation. However, tetracyclines are unstable when exposed to UV radiation, which can lead to photodegradation of the drug, causing toxicity or loss of efficacy. Clays are natural materials with favorable physicochemical properties for use in pharmaceutical formulations. The ability to reflect solar radiation and the presence of channels or lamellae can promote the photoprotection of the drug when incorporated into the structure. This work aimed to investigate the photostability of hybrids formed by incorporating drugs from the tetracycline family (OTC and DTC) into fibrous and lamellar clays and to evaluate the antibacterial activity of the hybrids before and after exposure to 200 h of radiation. For this work, four types of clay were used: VHS, Veegum, Paligorsquita, and Sepiolita, which were used without prior purification. The adsorption of each system was carried out using 2g of clay in 2g/L of the drug under the agitation of 136 rpm at 25 °C in one hour of reaction. The radiation stability tests were conducted under a 125W mercury vapor lamp without a bulb. The samples were irradiated in petri dishes for up to 200 hours. This system was monitored using X-ray diffraction (XRD), thermogravimetric analysis (TG-DTG), BET, Transmission Electron Microscopy (TEM), and Fourier Transform Infrared Spectroscopy (FTIR). Microbiological tests were then carried out to assess the antibacterial activity of the irradiated and non-irradiated hybrids. The results showed greater incorporation of the antibiotic into lamellar clay minerals than into clay minerals with a fibrous morphology. The irradiation tests observed minimal degradation of the adsorbed drug molecules, probably due to the strong interactions between the organic and inorganic structures. In the biological tests, all the hybrids' antibacterial activity was investigated against Gram-positive cocci strains and Gram-negative bacillary bacteria. For both bacteria, Staphylococcus aureus and Escherichia coli, all systems (drug/clay) showed 100% inhibition of colony growth. A slight decrease in antibacterial potential was observed for the irradiated systems, and for Gram-positive bacteria, this variation was not significant. Thus, the experiments showed that clay minerals are suitable for stabilizing drug molecules and exhibit excellent antibacterial activity, especially against Staphylococcus aureus strains. Thus, the complexes are promising for applications as photoprotection agents for drugs.