Purpose: To explore whether baseline matrix metalloproteinase (MMP)-8 level in gingival crevicular fluid (GCF) (exposure) can predict the outcome (reduction in probing pocket depth (PPD) (outcome)) of nonsurgical periodontal therapy (NSPT) (manual or ultrasonic or both) in patients with periodontitis (population/problem) after 3 months. Methods: Six databases (PubMed, Cochrane library, ProQuest, Ovid, Scopus, EBSCO) were searched for relevant articles published until 30 July 2021. Retrieved articles were passed through a three-phase filtration process on the basis of the eligibility criteria. The primary outcome was the change in PPD after 3 months. Quality of the selected articles was assessed using Cochrane Risk of Bias tool (RoB2) and Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tools. Results: From 1306 articles, five were selected for analysis. The results showed high variations in the level of GCF MMP-8 level at baseline. The average amount of reduction in PPD was 1.20 and 2.30 mm for pockets with initial depth of 4–6 mm and >6 mm, respectively. Conclusion: On the basis of available evidence, it was not possible to reach a consensus on the ability of baseline GCF MMP-8 to forecast the outcome of NSPT. This could have been due to variation in clinical and laboratory techniques used. However, consistency in mean PPD reduction after 3 months was shown.
