This study focused on whether the effectiveness of nonsurgical periodontal therapy (NSPT) on second molars (M2s) varies with the status of adjacent nonimpacted third molars (N-M3s). In this retrospective cohort study, 776 regions from 268 patients were evaluated. Based on the adjacent N-M3 status, quadrants with M2s were categorized into three groups: N-M3 group (present N-M3), A-M3 group (absent M3), and R-M3 group (removed N-M3). The probing depth reduction (ΔPD) and the percentage of reversed deep pockets (PD5+ [probing depth ≥5 mm] turned to PD5-) after NSPT were analyzed among the three groups. The Wilcoxon nonparametric test was employed to compare the N-M3 group with the A-M3 group, with a mixed-effect model utilized to adjust for confounding factors. Further, the R-M3 group and the matched N-M3 group were compared using the Wilcoxon nonparametric test. After isolating confounding factors (M2 baseline gingival recession, tooth mobility, sex, and follow-up interval), the ΔPD of M2s was significantly lower in the N-M3 group (0.93 ± 1.25 mm) compared with the A-M3 group (1.09 ± 1.30 mm, p < 0.001). Moreover, the percentage of reversed deep pockets in the N-M3 group (35.56%) was lower than in the A-M3 group (42.98%, p<0.001). Similarly, compared with the N-M3 group, M2s in the R-M3 group manifested better outcomes in terms of periodontal indices. Retained N-M3s may hamper the outcome of NSPT on adjacent M2s. Additionally, the removal of N-M3 is associated with an enhanced response of M2s to NSPT. The second molar is crucial for chewing, but it is often lost due to periodontitis. Periodontal treatment for the second molar is not always effective, and many factors contribute to this. One factor that has gained attention is the impact of a nonimpacted third molar on the periodontal health of the adjacent second molar. In this study, we examined how the presence of a nonimpacted third molar affects the outcome of nonsurgical periodontal therapy for the second molar. We analyzed 776 second molars from 268 patients. The results showed that when the nonimpacted third molar was absent or removed during periodontal therapy, the second molar's condition improved more than when the nonimpacted third molar was present. The data indicated that even with nonsurgical periodontal treatment, the periodontitis of the second molar could not be effectively controlled if an adjacent nonimpacted third molar was present. Therefore, the negative impact of the nonimpacted third molar should be considered to prevent the loss of the second molar.