Oral diseases, chiefly dental caries, gingivitis, periodontitis, and halitosis, continue to top the list of global health burdens. The 2021 Global Burden of Disease analysis estimated that 3.7 billion people live with at least one untreated oral condition; dental caries in permanent teeth alone remains the single most prevalent ailment worldwide, while severe periodontitis ranks among the leading causes of years lived with disability [1]. Apart from causing pain and tooth loss, these infections are increasingly linked to systemic problems such as diabetes, atherosclerotic heart disease, and adverse pregnancy outcomes, highlighting the need for more effective prevention methods.

At the core of plaque-related disease is a structured, multispecies biofilm that firmly adheres to tooth and mucosal surfaces [2]. Since mechanical brushing and flossing often do not fully penetrate the deepest layers of this extracellular polymeric matrix, chemical adjuncts and mouthwashes now play a crucial role in both home care and professional advice [3,4]. Chlorhexidine (CHX) gluconate has long been regarded as the gold standard due to its broad antimicrobial spectrum and substantivity; essential-oil (EO) rinses (thymol, eucalyptol, menthol) and cetylpyridinium chloride (CPC) provide alcohol-based or alcohol-free options, while fluoride, xylitol, zinc salts, and various herbal extracts are included for remineralization, anti-malodour, and xerostomia relief [[5], [6], [7]].

Although widely used clinically for decades, traditional rinses have known drawbacks. Frequent CHX use can cause extrinsic tooth staining, taste changes, and supragingival calculus buildup, often within 4 weeks of daily use [[8], [9], [10]]. Alcohol-based vehicles can cause mucosal irritation and worsen xerostomia; repeated doses above the minimum inhibitory concentration (MIC) of broad-spectrum biocides risk oral dysbiosis and reduce patient adherence [[11], [12], [13]]. Most importantly, the relatively large molecular size of these actives and the lack of active-penetration mechanisms restrict their ability to reach bacteria deep within mature biofilms, leaving behind residual viable communities that quickly recolonize cleaned surfaces [14,15].

Nanotechnology offers a mechanistic approach to overcoming these limitations. Nanoparticles (1-100 nm) have large surface-area-to-mass ratios, tunable surface charges, and easily adjustable coatings, allowing formulators to create pH-triggered, enzymatic, or slow-release mouthrinses. First, sub-10 nm silver nanoparticles (AgNPs) pass through the extracellular polymeric substance of mature dental plaque, delivering localized oxidative stress and Ag+ toxicity directly to protected microbes, thereby achieving biofilm kill rates comparable to or higher than those of CHX at much lower doses [[16], [17], [18]]. Second, multifunctional nanocarriers, such as chitosan or zinc oxide particles, offer inherent antimicrobial and antiinflammatory properties, while their mucoadhesive surfaces enhance retention. Similarly, bioactive glass nanospheres gradually release calcium and phosphate ions, thereby promoting in situ enamel remineralization [[19], [20], [21]]. Finally, the high surface reactivity of nano-enabled formulations provides a dose-sparing benefit, enabling similar or better antibacterial results at lower concentrations of the bulk drug. This reduces the risk of taste disturbances, staining, and systemic absorption while maintaining the oral microbiome [22]. A growing body of evidence supports these theoretical advantages. A recent double-blind, randomized controlled trial in orthodontic patients demonstrated that a 5 nm AgNP mouthrinse was as effective as 0.2 % CHX in reducing microbial colonization and gingival bleeding scores, with no noticeable staining or taste issues after 8 weeks [23]. In another clinical study, a chitosan-silver-fluoride nanocomposite rinse significantly reduced salivary Streptococcus mutans levels and improved pH balance, while exhibiting lower cytotoxicity than commercial CHX [20]. Preclinical models have also demonstrated that applying AgNP rinses after extraction or mucogingival surgery accelerates wound closure and re-epithelialization, suggesting additional benefits for oral soft-tissue healing [24].

Despite these encouraging findings, significant knowledge gaps still exist. Published studies differ significantly in terms of particle size, surface functionalization, concentration, dosing schedules, and assessment endpoints, making cross-study comparisons challenging. Long-term safety data are limited; nano-silver, in particular, shows size- and coating-dependent cytotoxicity, genotoxicity, and environmental persistence that warrant careful consideration against its clinical benefits [25]. Regulatory frameworks for nano-enabled oral care products are still in development, and there is no consensus on standardized physicochemical characterization or in-use stability testing.

Given the ongoing global burden of plaque-related diseases, limitations of traditional rinses, and the rapid rise in nano-mouthwash patents and publications since 2020, a comprehensive synthesis of current evidence is both timely and necessary. While previous reviews have examined various aspects of nanotechnology in oral care, including applications of specific nanoparticles like silver, zinc oxide, and nano-hydroxyapatite in dental materials and mouthwashes, none have comprehensively integrated clinical trial evidence, preclinical mechanistic studies, and patent literature to provide a holistic understanding of nano-enabled mouthwashes' efficacy, safety, and commercial landscape. Earlier systematic reviews have primarily focused on individual nanoparticle types, regenerative applications, or broader dental nanotechnology applications without specific emphasis on mouthwash formulations. This represents a significant gap in the literature, as the convergence of clinical effectiveness data, mechanistic insights from laboratory studies, and innovation trends from patent analysis is essential for guiding evidence-based clinical adoption and future research priorities in this rapidly evolving field [[26], [27], [28], [29], [30], [31], [32]]. This study aims to (i) catalog the physicochemical properties of nano-mouthwash formulations reported from January 2018 to June 2025, (ii) evaluate their antimicrobial, antiinflammatory, and remineralizing effects in vitro and in vivo, (iii) review reported adverse events and toxicology profiles, and (iv) identify methodological gaps and regulatory challenges to guide future product development and clinical research. By integrating a qualitative review of formulation features and safety data, this work seeks to provide clinicians, researchers, and industry stakeholders with an evidence-based resource for the rational development of nanoparticle-based mouthwashes in modern oral healthcare.