Drug delivery systems based on natural drug carriers have become important due to their non-toxicity and biodegradability. We report here the synthesis and characterization of new biomaterials like sponges containing collagen, chloramphenicol and glutaraldehyde for dentistry. All sponges favour water absorption, showing that increasing the glutaraldehyde content leads to an increase in water uptake. The sponges showed resistance to collagenase degradation and strong activity against the tested bacteria. Kinetic data showed non-Fickian diffusion behaviour with a slow release rate. Taking into account that dental drug delivery systems exhibit low water absorption, slow drug release, high content of drug delivery, good antimicrobial activity, and resistance to enzymatic action, the results obtained in this study indicate the optimal content of glutaraldehyde for the sponge as being 0.5%. The properties of the designed formulations demonstrate that these sponges could be adequate for the treatment and/or the prophylaxis of infected lesions at the dental level.