Successful treatment of endodontic and periapical diseases requires the elimination of bacteria and micro-bial biofilms from root canals.Currently,the most preferred irrigation method involves the delivery of sodium hypochlo-rite via the combination of a syringe and ultrasonic activation.Calcium hydroxide is the main choice for intracanal medi-cament between endodontic appointments and treatment.However,conventional chemical disinfection of root canals is controversial due to drug permeability and drug resistance.New small biomolecule formulations with high penetrability and bioremediatory capacity,including antimicrobial peptides such as M33D and LL-37,antisense RNA ASwalR/ASvicR and nanoparticles such as silver nanoparticles,mesoporous calcium-silicate nanoparticles and chitosan nanoparticles,have effective antibacterial and antibiofilm properties for use in root canal systems and dentinal tubules,thereby promot-ing the healing of apical lesions.However,the in vivo drug stability,biosafety,and clinical efficacy of small biomolecule formulations need further investigation.Future research will still focus on the improvement and combination of tradition-al drugs,as new small molecule formulations and ideal disinfectant drugs need to be developed.In the present paper,we reviewed the development of new antibacterial agents and application of small biomolecule formulations for chemical disinfection of infected root canals.