Background: This systematic review aimed to assess the outcomes related to the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to non-surgical periodontal treatment (NSPT) of patients affected by periodontitis and with type 2 diabetes mellitus (T2DM). Methods: PubMed, Cochrane Library, Scopus, and Web of Science (core collection) were queried up to January 2025. The PICO question investigated the comparison between T2DM patients undergoing NSPT with or without aPDT, in terms of improvement of clinical parameters. Two independent operators performed the study selection, data extraction, and risk of bias assessment (RoB-2 tool). The meta-analysis examined the reduction in bleeding on probing (BoP) and probing pocket depth (PPD) in sites > 4 mm, reporting mean difference (MD) and 95% confidence intervals (CIs). Results: Among 502 studies retrieved, 15 were finally included in the systematic review and meta-analysis. In T2DM individuals, the adjunct of aPDT to NSPT demonstrated a substantial reduction in BoP and PPD after 3 and 6 months compared to the use of NSPT alone. Conclusions: The outcomes of this systematic review suggest that adjunctive aPDT may provide additional benefit to NSPT in reducing inflammation in T2DM patients with periodontitis, indicating that this combined therapy could represent a potentially useful approach for individuals with T2DM. Review registration: registration in PROSPERO (International prospective register of systematic reviews) with ID CRD42024506295 on 6 February 2024.