Objective This study aimed to evaluate the efficacy of antimicrobial photodynamic therapy (aPDT) and systemic antimicrobial drug as an adjunct treatment for periodontitis. Methods Seven databases, namely, Embase, PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP, were searched from inception until November 2023. The language of the searched literature is Chinese or English. Studies were screened out according to inclusion and exclusion criteria, and their quality was evaluated using the Cochrane tool. Meta-analysis and publication bias detection of the included studies were performed using RevMan 5.4 and Stata 14.0 software. Results Eight studies were included. Meta-analysis showed that 3 months after treatment using methylene blue (MB) as the photosensitizer (PS), the improvement effect of scaling and root planning (SRP)+aPDT on probing depth (PD) was better than that of SRP+systemic antimicrobial drug. When phenothiazine chloride was the PS, the improvement effect of SRP+systemic antimicrobial drug on PD was better than that of SRP+aPDT (P<0.05). No significant difference was observed in the improvement effect of SRP+aPDT/SRP+systemic antimicrobial drug on clinical attachment level (CAL) and probing bleeding (BOP) at 3 months after treatment (P>0.05) and the improvement effect of SRP+aPDT/SRP+systemic antimicrobial drug on PD, CAL, and BOP at 6 months after treatment (P>0.05). Compared with those at baseline, SRP+aPDT improved PD, CAL, and BOP by (0.80±0.19) mm, (0.94±0.29) mm, and 19.74%±1.91%, respectively, at 3 months after treatment (P<0.05). In addition, SRP+systemic antimicrobial drug improved PD, CAL, and BOP by (1.02±0.27) mm, (0.95±0.25) mm, and 19.39%±11.83%, respectively (P<0.05). At 6 months after treatment, SRP+aPDT improved PD, CAL, and BOP by (1.37±0.47) mm, (1.29±0.52) mm, and 28.97%±2.43%, respectively (P<0.05). In addition, SRP+systemic antimicrobial drug improved PD, CAL, and BOP by (1.55±0.53) mm, (1.34±0.49) mm, and 29.34%±10.47%, respectively (P<0.05). Conclusion For PD, the improvement effect is in the order of SRP+MB-aPDT>SRP+systemic antimicrobial drug> SRP+phenothiazine chloride-aPDT. MB-aPDT may be an alternative to systemic antimicrobial drug as an adjunct treatment for periodontitis. The type of periodontitis, type 2 diabetes mellitus, smoking, number of aPDT, type of systemic antimicrobial drug, and treatment time of systemic antimicrobial drug have a similar influence on the treatment effect of SRP+aPDT/SRP+systemic antimicrobial drug.