Introduction: Periodontitis is a multifactorial chronic inflammatory disease induced by a dysbiosis between the host and oral microbiota, which can compromise the host’s immune defenses and lead to the destruction of periodontal tissues. Despite the efficacy of non-surgical periodontal therapy (NSPT) as the gold standard of periodontal treatment, its application can produce lower results due to anatomical and microbiological limitations. This systematic literature review was performed to assess the long-term efficacy of the effects of probiotics as an adjunct to NSPT compared to the control groups with follow-up of clinical, microbiological and immunological outcomes. Materials and methods: A literature review was conducted, considering manuscripts published from November 2016 to February 2022. The research question was formulated following the population, intervention, comparison and outcome strategies. Randomized controlled trials (RCT), systematic review and meta-analysis investigating the periodontal efficacy of domiciliary probiotic therapy in an adjunct to the mechanical therapy were included. Results: Regarding clinical outcomes, there is a reduction in periodontal probing depth (PPD), clinical attachments level (CAL), bleeding on probing (BoP) and plaque index (PI) for the test groups compared to the control groups in a short-term period. No differences were generally observed in the following indices over a period of more than 3 months for most studies considered. Conclusions: Weak evidence suggests that the use of probiotics as an adjunct to non-surgical periodontal therapy treatment may be able to show improvements in periodontal clinical parameters for up to 3 months. However, a significant and large heterogeneity of studies, along with the absence of long-term microbiological and immunological data, preclude any definitive conclusions.