Periodontal disease remains a major worldwide oral health problem, affecting about 538 million people all around the globe. It is caused by changes in local microflora inhabiting the plaque biofilm from Gram-positive to Gram-negative facultatively anaerobic bacteria, destroying the periodontal membrane and surrounding alveolar bone. Mechanical debridement of biofilm and antibiotics has been used as conventional therapy for gingivitis and periodontitis. However, the uncertain efficacy of the current treatment leads to using probiotics as a promising strategy to combat the periodontal pathogen. An antibiotic application might contribute to antimicrobial resistance and environmental pollution due to non-degradable residue. Probiotics could be an alternative treatment for periodontal disease. This meta-analysis study aims to assess the potential of probiotic bacteria to reduce the magnitude of the inflammatory response, especially in the pro-inflammatory cytokines. Electronic databases such as Google Scholar, Science Direct, and PubMed were used to search for related articles up to May 2021. Randomized Controlled Clinical Trials (RCTs) or controlled clinical trials were included in the study, whereby the concentration of IL-1β and TNF-α were chosen as the main outcome variables. Independent screening resulted in four eligible publications being included in the meta-analysis. However, the overall mean difference for the concentration of IL-1β (MD: -0.32; 95% CI: -1.88, 1.25; P = 0.69) and TNF-α (MD: 0; 95% CI: -0.20, 0.20; P= 0.98) did not show any statistical significance difference between probiotic and placebo groups. Therefore, the study results demonstrated weak evidence to support the usage of probiotics in reducing the magnitude of inflammatory response in patients with periodontal disease. Smaller sample sizes and limited available data may contribute to this conclusion. Hence, future randomized controlled clinical trials with larger sample sizes and a longer intervention period must be considered to evaluate the efficacy of probiotics in periodontal disease.