Introduction. The study investigated the effect of weekly supragingival irrigation with aerosolized 0.5% hydrogen peroxide (H2O2) solution as a maintenance periodontal therapy on clinical and microbiological parameters in patients with chronic periodontitis. The other purpose was to investigate whether cavitation bubbles can penetrate not only into periodontitis-damaged tissues but also into ex vivo porcine healthy periodontal tissues. Materials and Methods. The study included 35 systemically healthy patients with chronic periodontitis (CP). After nonsurgical periodontal debridement (NSPD), all patients were randomized into two groups: the Control group (NSDP alone, n=18) and the Test group (NSDP plus supragingival irrigation, n=17). Clinical (Approximal Plaque Index (API), Bleeding Index (BI), and Modified Gingival Index (MGI)) and microbiological (Polymerase Chain Reaction technology (using a micro-IDent® kit)) measurements were performed at the initial time point, 3 months, and 6 months after NSPD. The impact of supragingival irrigation on diseased gingival tissues of CP patients (n=5) and on ex vivo porcine healthy gingival tissue samples (n=3) was evaluated to estimate morphological changes in healthy and diseased gingival tissues. Results. Morphological data revealed that supragingival irrigation caused the formation of cavitation bubbles in diseased gingival tissue of CP patients and in healthy porcine gingival tissues. The decrease in API, BI, and MGI scores after 6 months in the Test group significantly (p≤0.01, p≤0.05, and p≤0.01, respectively) exceeded that in the Control group. Test group patients demonstrated a decrease in periodontal sites showing Pocket Probing Depth>4 mm and, after 6 months, a statistically significant decrease in the proportion of periopathogenic bacteria. Conclusion. The effectiveness of mechanical periodontal treatment combined with weekly supragingival irrigation with aerosolized 0.5% H2O2 solution on clinical and microbiological parameters of periodontal tissues of periodontitis patients is reliably higher than that of mechanical periodontal debridement alone. It has been found that cavitation bubbles as a result of irrigation with the aerosolized 0.5% hydrogen peroxide solution can form not only in periodontal tissues of periodontitis patients but also in ex vivo porcine healthy gingival tissues.