Objective To compare the effectiveness of the laser, drug and laser combined with drug in the repair of combined periodontal-endodontic lesions. Methods A total of 160 cases of combined periodontal-endodontic lesions were randomly divided into basic treatment group, laser treatment group, drug treatment group and combined treatment group. Patients in the basic treatment group were only treated with standard treatment (root canal and systemic periodontal treatment). Patients in the laser treatment group received additional semiconductor laser therapy. Patients in the drug treatment group were treated with additional Minocycline Hydrochloride Ointment. Patients in the combined treatment group were treated additionally with laser combined with Minocycline Hydrochloride Ointment. Changes of periodontal pocket depth, bleeding index, clinical attachment level, tooth mobility, plaque index and gingival index were observed before and after treatment. The total efficiency of the four groups was compared. Results The depth of periodontal pocket, improved bleeding index, clinical attachment level after 6 months of treatment were all lower than those before treatment in the four groups (P < 0.01). The periodontal pocket depth, modified bleeding index, clinical attachment level, tooth mobility, plaque index and gingival index in the combined treatment group after treatment were lower than those in the other three groups (P < 0.01). The indexes of the laser treatment group and the drug treatment group were significantly lower than those in the basic treatment group (P < 0.01). The total effective rate of treatment in the combined treatment group was higher than that of the basic treatment group (P < 0.05). Conclusions The effect of laser combined with drugs in the treatment of combined periodontalendodontic lesions is better than that of only laser or drug assisted treatment, which is worth popularizing.