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The aim of this review was to examine which cross\u2010linking agent performs better in reducing root caries lesion depth and the release of hydroxyproline, which is a marker of collagen degradation. Studies evaluating the impact of cross\u2010linking agents on dentin were included, while studies performed on enamel surface\/cell cultures and studies evaluating collagenase inhibitors were excluded, among others. A comprehensive search covered eight databases, and study quality was assessed using the QUINN Tool for in vitro dental studies. Synthesis of the results was done using a Bayesian network meta\u2010analysis to compare agents. Fifty studies involving 31 cross\u2010linking agents were included for qualitative synthesis. The network meta\u2010analysis for lesion depth involved 284 samples across 36 comparisons and ranked cross\u2010linking agents in terms of their caries lesion depth\u2010reducing effect (from best to worst): naringin\u00a0&gt;\u00a0quercetin\u00a0&gt;\u00a0riboflavin\u00a0&gt;\u00a0proanthocyanidins\u00a0&gt;\u00a0hesperidin\u00a0&gt;\u00a0glutaraldehyde\u00a0&gt;\u00a0cranberry\u00a0&gt;\u00a0grape seed extract\u00a0&gt;\u00a0untreated controls. Only naringin, quercetin, proanthocyanidins, and glutaraldehyde showed statistically significant efficacy over untreated controls. Cranberry extract excelled in reducing hydroxyproline release, followed by proanthocyanidins. In conclusion, proanthocyanidins positively affected both outcomes, suggesting they are prime candidates for translational research. Clinical studies are now essential to evaluate their real\u2010world effectiveness against root caries. 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