Purpose: This randomized, controlled clinical trial aimed to evaluate the clinical, adjunctive effects of an approved botanical barrier device or patch on probing parameters in patients with periodontitis. Materials and Methods: Eighty patients with periodontitis were recruited for this single-blinded trial. Patient demographic data, including gender, age, self-reported smoking status, and history of diabetes or cardiovascular disease, were collected. At baseline, all patients received a full-mouth probing examination followed by scaling and root planing (SRP). Thereafter, patients were randomized to receive either adjunctive botanical patch applications (i.e. at 2–4 treatment sites with baseline pocket depth PD ≥6 mm) or no additional therapy (SRP alone, control). Patients applied botanical patch devices per randomization to treatment sites three times on day 0 and once daily on days 1–6. Study devices were spontaneously shed or removed by the patient at 2–2.5 h after each application. Patients were recalled for probing reexaminations at 1, 2 and 3 months. Statistical analyses focused on intergroup differences in probing parameters and included ANOVA for baseline measures and ANCOVA controlling for baseline measures at 1, 2 and 3 months in the overall population and in subpopulations (e.g. smokers vs nonsmokers). Results: Randomized patient groups were balanced with respect to baseline periodontal status (mean and extent PD) but not smoking, with statistically significantly more smokers clustering in the control group (p = 0.002). For the overall population and the non-smoking subpopulation, statistically significantly improved PD and clinical attachment levels (CAL) were observed with adjunctive botanical patch therapy vs control at 1 and 2 months (p < 0.05) but not 3 months (p = 0.08 for PD). For smokers, no statistically significant intergroup differences in PD or CAL were detected with botanical patch treatment. Conclusions: The data from this trial indicate short-term improvements in probing parameters with the botanical patch device when used adjunctively with SRP, especially with non-smoking periodontitis patients.