BackgroundThis study was designed to assess the influence of non‐surgical periodontal therapy (NSPT) on gingival crevicular fluid (GCF) levels of semaphorin‐4D (SEMA‐4D), peptidylarginine deiminase‐2 (PAD‐2), and matrix metalloproteinase‐8 (MMP‐8) levels in periodontally healthy, Stage III periodontitis non‐smoker and smoker patients.MethodsSixty patients were equally divided into three groups, Group I: Periodontally healthy, Group II: Non‐smokers with Stage III periodontitis, and Group III: Smokers with Stage III periodontitis. The patients underwent NSPT with clinical and biochemical parameters examined at baseline and 3 months post therapy. GCF was collected for levels of SEMA‐4D, PAD‐2, and MMP‐8 through enzyme‐linked immunosorbent assay (ELISA).ResultsGreater values of PPD (8.06 ± 0.19 mm), CAL (8.94 ± 0.19 mm), PI (2.58 ± 0.19) while lower PBI (1.39 ± 0.19%) and GI (1.72 ± 0.19) scores were seen in Group III as compared to Group II, which reduced significantly from baseline to 3 months in both the groups after NSPT. Minimum values of SEMA‐4D, PAD‐2, and MMP‐8 levels in GCF were seen for Group I, which increased incrementally to Group II and III. Also, among Group II and III the SEMA‐4D, PAD‐2, and MMP‐8 levels in GCF reduced from baseline to 3 months indicating a favorable response within the tissues.ConclusionGreater levels in GCF of Levels of SEMA‐4D, PAD‐2, and MMP‐8 in Group II and III, which reduced significantly post NSPT, implied that these biomarkers play a pivotal role in the inflammatory process and can be utilized for early diagnosis.