Clinical research on herbal-based dentifrice +/- mouth rinse products is very limited compared with the plethora of research on conventional oral care products under normal oral hygiene conditions. The aim of this study was to determine the anti-inflammatory effects of a novel plant Carica papaya leaf extract (CPLE) on interdental bleeding in healthy subjects. In this randomized, single-blind parallel-design study, the eligible subjects were generally healthy non-smokers, aged 18⁻26, who exhibited healthy periodontal conditions upon study entry. The participants were equally randomized into the following four groups: CPLE dentifrice, CPLE dentifrice and mouthwash, sodium lauryl sulfate (SLS)-free enzyme-containing dentifrice and SLS-free enzyme-containing dentifrice with essential oil (EO) mouthwash. Subjects were instructed to brush their teeth twice a day without changing their other brushing habits. Interdental bleeding (BOIP) was measured from inclusion (T₀) until the fourth week (T₄) of the study. Clinical efficacy was assessed after one, two, three and four weeks of home use. The analyses compared BOIP between groups and were then restricted to participants with ≥70% and then ≥80% bleeding sites at T₀. Pairwise comparisons between groups were performed at T₀ and T₄, and a logistic regression identified correlates of gingival bleeding (T₄). Among 100 subjects (2273 interdental sites), the median percentage of bleeding sites per participant at T₀ was 65%. The bleeding sites dramatically decreased in all groups between T₀ and T₄ (relative variations from -54% to -75%, p < 0.01 for all). Gingival bleeding did not significantly differ between the CPLE dentifrice and the SLS-free dentifrice +/- EO mouthwash groups (from p = 0.05 to p = 0.86), regardless of the baseline risk level. Among the CPLE dentifrice users, fewer bleeding sites were observed when toothpaste and mouthwash were combined compared to bleeding sites in those who used toothpaste alone (21% vs. 32%, p = 0.04). CPLE dentifrice/mouthwash provides an efficacious and natural alternative to SLS-free dentifrice +/-EO-containing mouthwash when used as an adjunct to mechanical oral care to reduce interdental gingival inflammation.