Objective This study used a retrospective method to explore the relevant factors affecting the prognosis of periodontal-endodontic combined lesions. Methods According to the changes of subjective feelings and clinical indicators of affected teeth, selected patients were divided into an effective group and an ineffective group. The natural conditions (age, gender, and smoking status) of the patients and various clinical indicators at the initial and follow-up visits were collected, including the periodontal clinical indicators of the whole mouth and the clinical indicators of the affected teeth. The full-mouth periodontal clinical indicators include periodontal probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI), and simplified oral hygiene index (OHI.S); clinical indicators of affected teeth include PD, CAL, SBI, mobility (TM), clinical crown-to-root ratio (CR), periapical index (PAI), and number of root canals. Results There were 74 cases of endodontic combined treatment, with a total of 86 teeth. There was no significant difference in age and gender ratio between the effective group and the ineffective group, and the proportion of smoking patients in the ineffective group was significantly higher than that in the effective group (P < 0.05). At the initial diagnosis, there was no significant difference in the clinical indicators of the whole mouth between the effective group and the ineffective group. After a combined endodontic treatment, the clinical indicators of the two groups were significantly improved (P < 0.01). There was no significant difference in other periodontal clinical indicators between the two groups. Conclusion The prognosis of nonsurgical treatment of periodontal and periodontal combined lesions is mainly correlated to the patient's oral hygiene maintenance, as well as the loss of attachment, the degree of loosening, the clinical crown-to-root ratio, the periapical index, and the number of root canals.