BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and microbiological effect of photodynamic therapy (PDT) in the non-surgical treatment of periodontitis in HIV patients. METHODS: Twelve HIV patients from the CEAPE/UNIP, Brazil, with periodontitis were included in this 6-month, split-mouth, double-blind, controlled clinical trial. Patients were placed in the following groups: Group SRP-scaling and root planning with an ultrasonic device (SRP); and Group SRP + PDT-SRP associated with a course of PDT with a diode laser with a wavelength of 660 nm and 0.03 W power associated with methylene blue 0.01% lasting 133 seconds. All clinical measurements (periodontal probing depth (PPD), gingival recession (GR), clinical attachment level (CAL), full-mouth plaque index (FMPI), bleeding score (FMBS)), and microbiological parameters (detection of Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Aggregatibacter actinomycetemcomitans (Aa)) were assessed at baseline and at 45 days, and 3 and 6 months after therapy. The ANOVA/Tukey was used for statistical analysis (α = 5%). RESULTS: There were no differences in any of the investigated parameters observed at baseline in the two groups (P > 0.05). Moreover, participants in the SRP + PDT group presented a higher PPD reduction and CAL gain than those in the SRP group at 45 days and 3 and 6 months. At 6 months, sites receiving SRP + PDT showed a significant PPD reduction of 1.4 ± 0.5 mm, while those in the SRP group showed a 0.3 ± 0.8 mm reduction (P < 0.05). The CAL gain at the sixth month was 1.3 ± 0.5 mm and 0.2 ± 0.7 mm for participants in the SRP + PDT and SRP groups, respectively (P < 0.05). Microbiologically, both therapies presented a reduction in the detection of Pg, Tf, and Aa, and there was no difference between them (P > 0.05). CONCLUSION: We concluded that PDT therapy used adjunctively to SRP could promote additional benefits in the treatment of HIV-associated periodontitis.