Due to the complex anatomical structures of the root canal, thorough intracanal disinfection has always been challenging in endodontic treatment. Existing intracanal medicaments exhibit limitations such as low permeability and suboptimal antibacterial performance. Thus, an intracanal medicament that combines excellent operating performance with potent antibacterial properties is required. Therefore, we designed an injectable hydrogel loaded with modified triple antibiotic drugs (mTAD) through a Schiff base reaction of carboxymethyl chitosan (CMCS) and polyethylene glycol aldehyde (OHC-PEG-CHO), mTAD/CMCS/OHC-PEG-CHO (mTCP). We subsequently evaluated the characteristics of mTCP. Moreover, the antibacterial capacity of the hydrogels was assessed in vitro. The effects of mTCP on the cell biocompatibility and odonto-/osteogenic differentiation of stem cells from the apical papilla (SCAPs) were also examined. Furthermore, we established a periapical inflammation model in the young permanent teeth of a Beagle dog and explored the effects of mTCP on root canal disinfection and root development. Our findings revealed that mTCP exhibited excellent operability, fluidity, and ease of removal from the root canal. mTCP presented outstanding antibacterial efficacy both in vitro and in vivo, attributed to its exceptional permeability and sustained release of mTAD. The odonto-/osteogenic differentiation of SCAPs was augmented by adding mTCP. Moreover, mTCP facilitated root elongation, dentinal wall thickening, and apical closure in the Beagle dog model. mTCP exhibited a pronounced effect on promoting periapical tissue healing and root development. In conclusion, mTCP hydrogel has promising potential for root canal disinfection in endodontic therapy.