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The study aimed to investigate the effects of endodontic space decontamination using a laser combined with ozonated water in the therapy of complicated pulp gangrene. The subject of this in vivo study was a 12-year-old patient diagnosed with extensive periapical periodontitis on the mandibular right first molar. Biological samples were initially collected to identify the active pathogen—<i>Enterococcus faecalis</i>, then the nonsurgical endodontic treatment was performed in a single visit, according to the active disinfection guidelines of the identified pathogen. Two-month postoperative, clinical and radiological examination revealed a complete healing of the periapical lesion. The correct diagnosis of this endodontic–periodontal pathology, and the unconventional treatment of the complex system of infected root canals, allowed a favorable treatment result without any surgical intervention. This unconventional approach, which combines a laser technique with ozonated water, allows for predictable results in periapical lesion treatment.