In the present study, the impact of scaling and root planing (SRP) on gingival crevicular fluid (GCF) cytokine/chemokine levels in smokers with chronic periodontitis was assessed. The PICO (population, intervention, comparison, outcome) question was: In smokers with chronic periodontitis (population), what is the effect of SRP (intervention) in comparison to SRP in non-smokers with chronic periodontitis (comparison) on the GCF cytokine/chemokine level (outcome)? Indexed databases were searched up to September 2017. Of 4330 titles, nine studies reporting the levels of 13 different cytokines/chemokines were included. Eight studies had a moderate risk of bias, while one study had a high risk of bias. Almost all cytokines/chemokines were pro-inflammatory cytokines. Five cytokines/chemokines studied in four clinical studies were decreased in the smoker-chronic periodontitis group following SRP. One study observed that the GCF levels of interleukin-17 increased, while anti-inflammatory osteoprotegerin was reduced in both the SCP and non-smoker-chronic periodontitis groups at follow up. However, the majority of cytokines/chemokines did not change in the SCP groups at follow up. The current weight of evidence is not sufficient to prove that SRP has an impact on GCF cytokine/chemokine profile in smokers with chronic periodontitis. Evaluation of wide panels of pro-inflammatory cytokines/chemokines related to collagen degradation and alveolar bone destruction in future studies are warranted.