Objective: The purpose of this systematic review is to evaluate the available scientific literature on the effectiveness of combining sodium hypochlorite and cross-linked hyaluronic acid (xHyA) as an adjunct to non-surgical periodontal treatment. Materials and Methods: Five electronic databases were searched. The study was traced using the PRISMA criteria and publications from ProQuest, Google Scholar, Springer Nature, Scopus, and PubMed. The randomized study was examined using the Cochrane Risk of Bias 2 (RoB) tool and two case series studies were reviewed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Results: The systematic review included four studies (two RCT and two case series). Across the included studies, the adjunctive use of sodium hypochlorite/amino acid gel and cross-linked hyaluronic acid (xHyA) following subgingival instrumentation was associated with improvements in clinical periodontal parameters. Probing pocket depth (PPD) reduction ranged from 1.5 to 5.8 mm, clinical attachment level (CAL) gain ranged from 1.5 to 5.3 mm, and bleeding on probing (BOP) reduction ranged from 57.5% to 65.6%. The improvements were generally more pronounced in deeper periodontal pockets. Minor variations in intervention protocols were observed among studies. Conclusions: The adjunctive use of sodium hypochlorite and cross-linked hyaluronic acid in non-surgical periodontal therapy may be associated with improvements in clinical periodontal parameters, including PPD, CAL, and BOP, particularly in deep pockets. However, the available evidence is limited and heterogeneous, with small sample sizes and short follow-up durations. Therefore, these findings should be interpreted with caution, and further well-designed long-term studies are required. © 2026 by the authors.