Background: Periodontitis (PDT) has gained attention in the literature with the increase in life expectancy of people living with HIV on combined antiretroviral therapy (cART). Thus, the search for inflammatory biomarkers could be useful to understand the pathophysiology of chronic oral diseases in the cART era. Objective: The aim of this study was to evaluate the impact of non-surgical periodontal therapy (NSPT) on clinical parameters of PDT, Candida spp. count and expression of LF and HST in saliva and CGF of HIV-infected patients. Methods: Bleeding index (BI), probing depth (PD), clinical attachment level (CAL), colony-forming units (CFUs) of Candida spp, and lactoferrin (LF) and histatin (HST) levels were measured in saliva and GCF of both groups at three different times: baseline (before treatment), and 30 and 90 days after the NSPT. Clinical, mycological and immunoenzymatic analyses were also performed. Results: Twenty-two HIV-infected patients and 25 non-HIV-infected patients with PDT participated in the study. NSPT was effective in improving periodontal clinical parameters, including ≤ 4 sites with PD ≤ 5mm and BI ≤ 10%. No significant change in oral Candida spp. count occurred neither between the two groups nor during the time after the periodontal treatment. And the salivary and GCF levels of LF and HST seems not to be influenced by the NSPT. By contrast, except for salivary LF, HST and LF were shown to exhibit significantly higher levels in HIV-infected than in non-HIV-infected patients. Conclusions: NSPT was effective in improving periodontal disease parameters in HIV-infected patients, but do not affect lactoferrin and histatin-5 expression in saliva and ginvival crevicular fluid of HIV-infected patients.