Introduction: this study aimed to evaluate the antimicrobial and physicochemical properties of a commercial endodontic sealer modified by the addition of montmorillonite (MMT) nanoparticles loaded with two different drugs: chlorhexidine (CHX) or metronidazole (MET). Methods: 5 wt% MMT/CHX or MMT/MET nanoparticles were added to the sealer AH-Plus. The experimental materials were evaluated for drug release, antimicrobial activity, flow, flexural strength, and flexural modulus. Data were subjected to one-way ANOVA, Kruskal-Wallis, and Mann-Whitney tests. Results: The drug incorporation into MMT particles was 9% and 10% for CHX and MET, respectively. At 20 days after manipulation, 16.5% of the drug was released by the sealer with MMT/MET and 0.4% by MMT/CHX. The addition of both nanoparticles decreased the flow of materials, but they were still in compliance with ISO 6876-2012. The conversion, flexural strength, and flexural modulus of MMT/MET (87%, 37±7 MPa, 2.3 GPa) and MMT/CHX (78%, 29±2 MPa, 2.7 GPa) were similar in both groups but lower than in the control group (100%, 54±7 MPa, 4.0±0.7 GPa). Both experimental materials were able to form an inhibition halo for E. faecalis bacteria (CHX: 4.8±1.4 and MET: 4.0±1.6 mm), whereas the control group did not inhibit the microorganism. Conclusion: both formulations proposed as endodontic sealer presented effective antimicrobial activity and acceptable flow. The addition of MMT/CHX and MMT/MET particles decreased the conversion and mechanical properties, but further studies are required to clarify the clinical relevance of these properties.