Comparison Between Natural Products and Chlorhexidine in Non-Surgical Periodontal Therapy: A Systematic Review of Randomized Clinical Trials

Objectives: To evaluate the clinical effectiveness and safety of natural products compared with chlorhexidine (CHX) as adjuncts to non-surgical periodontal therapy (NSPT) in patients with periodontitis. Materials and Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (CRD420251133219). Electronic searches of PubMed, Scopus, and Web of Science were performed to identify randomized controlled trials (RCTs) published between 2020 and 2025. Eligible studies included adult patients with periodontitis treated with NSPT, comparing CHX-based products with natural formulations (mouthwashes, gels, irrigants, or dentifrices). Data extraction included product type, concentration, mode of application, follow-up duration, and primary periodontal outcomes. Study quality was assessed using the NIH Quality Assessment Tool. Results: Thirteen randomized controlled clinical trials met the inclusion criteria. Natural products such as Curcuma longa, Morus alba, Spirulina platensis, Propolis, Triphala, and Lycium barbarum demonstrated improvements in clinical attachment level (CAL) and probing pocket depth (PPD) comparable to those obtained with CHX, along with significant reductions in bleeding on probing (BoP) and plaque index (PI). Probiotic- and ozone-based treatments also showed favorable clinical outcomes, with faster healing and fewer adverse effects, such as tooth staining and taste alteration. Follow-up periods ranged from 14 days to 3 months. Conclusions: Natural products appear to be safe and effective alternatives to CHX when used as adjuncts to non-surgical periodontal therapy, providing comparable clinical benefits with a lower incidence of side effects. Nevertheless, further large-scale, long-term randomized trials are needed to standardize formulations and concentrations and to confirm the durability of these clinical effects.